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PubMed1992

Pharmacokinetic-interaction study of didanosine and ranitidine in patients seropositive for human immunodeficiency virus.

The potential pharmacokinetic interactions between didanosine, an acid-labile antiretroviral agent, and ranitidine, an H2-receptor antagonist, were evaluated by a crossover study of 12 male patients seropositive for the human immunodeficiency virus. Single oral doses of 375 mg of didanosine, formulated as a citrate-phosphate-buffered sachet, or of 150 mg of ranitidine were administered alone or in combination (ranitidine was given 2 h prior to didanosine). Serial blood samples and total urinary output were collected after each treatment and analyzed for didanosine and/or ranitidine by validated high-performance liquid chromatography-UV assay methods. Pharmacokinetic parameters were calculated by noncompartmental methods. There were significant increases in mean area under the curve from time zero to infinity and mean urinary recovery for didanosine given in combination with ranitidine compared with those for didanosine alone. There were no significant differences between didanosine coadministered with ranitidine and didanosine alone in the respective mean peak concentrations in plasma, times to peak, elimination half-lives, or renal clearances. The mean area under the curve for ranitidine given with didanosine was significantly less than that for ranitidine given alone. There were no significant differences between the mean peak concentrations in plasma, times to peak, elimination half-lives, renal clearances, or urinary recovery values for ranitidine coadministered with didanosine and values for ranitidine given alone. These data demonstrate that administration of didanosine 2 h after ranitidine will result in a minor increase in the bioavailability of didanosine. A modification in the dose of didanosine or ranitidine is not necessary if the dose of ranitidine precedes that of didanosine by 2 h.

Administration, Oral↗

PubMedDate not supplied

Ranitidine: a new H2-receptor antagonist.

The pharmacology, pharmacokinetics, clinical efficacy, adverse reactions, drug interactions, and dosage of ranitidine are reviewed; specific comparisons are made of this new H2-receptor antagonist with the older agent, cimetidine. Ranitidine is a potent inhibitor of gastric acid secretion whose chemical structure lacks the imidazole group previously believed to be essential for H2-receptor blocking activity. The new agent does not bind substantially to the cytochrome P-450 mixed-function oxidase system and does not penetrate the cerebrospinal fluid appreciably. Peak serum ranitidine concentrations occur within one to two hours after oral administration; approximately 50% of an oral dose reaches systemic circulation. There are at least three metabolites of ranitidine, but substantial fractions of both i.v. and oral doses are recovered unchanged in the urine. Ranitidine's duration of action is 8-12 hours. Controlled clinical trials have shown ranitidine to be effective in the treatment of duodenal and gastric ulcers, Zollinger-Ellison syndrome, and prophylaxis against aspiration during anesthesia. Ranitidine has been effective in patients unresponsive to or intolerant of cimetidine. In clinical trials, the incidence of adverse effects from ranitidine has been low; certain rare but serious side effects that have been noted with cimetidine have not been associated with ranitidine therapy. There is no evidence thus far that certain drug-drug interactions observed with cimetidine therapy will occur with ranitidine. Oral adult daily doses of ranitidine are likely to be 300 mg given as the hydrochloride salt in two divided doses. Ranitidine is similar to cimetidine in efficacy but has an apparently safer adverse-effects profile. Ranitidine is likely to be the preferred agent in certain clinical situations.

Anesthesia↗

PubMedDate not supplied

Bile flow but not enterohepatic recirculation influences the pharmacokinetics of ranitidine in the rat.

Secondary peaks in oral concentration-time profiles following ranitidine administration may be due to discontinuous absorption along the gastrointestinal tract, postabsorptive storage and release, and/or enterohepatic recirculation (ER). The suitability of the rat as an animal model for studying mechanisms of the double peaks, and the relationship between ER and the occurrence of secondary peaks in ranitidine concentration-time profiles, were examined in the present investigation. Male Sprague-Dawley rats received ranitidine by oral gavage (50 mg/kg), and blood was collected at various times for 6 hr after dosing. Eight rats with chronic bile duct and jugular vein cannulae received ranitidine with bile flow intact or interrupted in a randomized complete cross-over design. Bile duct-cannulated (BDC) rats were divided into two groups: four rats received ranitidine immediately after bile flow interruption, and four rats received ranitidine 3 hr after bile flow interruption. Blood and bile were analyzed for ranitidine by HPLC. The area under the ranitidine concentration-time profile, the maximum serum ranitidine concentration, the time of maximum concentration, the fraction of ranitidine absorbed at each blood sample, biliary clearance, and the percentage of the dose recovered in bile as ranitidine were determined. Results indicated that the rat is an appropriate model for studying mechanisms responsible for the double peaking phenomenon. Multiple peaks or plateaus were observed in the ranitidine concentration-time profiles of all rats after oral administration with bile flow intact. Secondary peaks were evident in only two concentration-time profiles of BDC rats when bile flow was interrupted. Less than 3% of the dose was recovered in the bile as ranitidine or metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

The influence of ranitidine on the pharmacokinetics and toxicity of doxorubicin in rabbits.

The influence of ranitidine on the pharmacokinetics and toxicity of doxorubicin was studied in six female New Zealand white rabbits. Plasma pharmacokinetic data were first obtained from rabbits given 3 mg/kg doxorubicin. After 1 month, the same rabbits were treated with ranitidine, 2.5 mg/kg or 25 mg/kg, before and during doxorubicin administration. The plasma doxorubicin assays to determine pharmacokinetic parameters were repeated. Drug toxicity was evaluated using complete blood counts, and hepatic function was measured using a 14C-aminopyrine breath test. High-dose ranitidine increased the total exposure to doxorubicin (area under the curve of doxorubicin alone = 1.44 +/- 0.88 microM.h/ml vs 4.49 +/- 2.35 microM.hr/ml for doxorubicin given with high-dose ranitidine; P = 0.06). Low-dose ranitidine did not alter doxorubicin pharmacokinetics. Exposure to doxorubicinol was altered by either high-dose or low-dose ranitidine. 14C-Aminopyrine half-life was altered by a ranitidine dose of 25 mg/kg (aminopyrine half-life after placebo control = 97 +/- 6 min as against aminopyrine half-life after ranitidine = 121 +/- 7 min; mean +/- SEM; P less than 0.02). Low-dose ranitidine did not exacerbate doxorubicin-induced myelosuppression. High-dose ranitidine enhanced doxorubicin-induced erythroid suppression while sparing the myeloid series. At cytochrome P-450-inhibitory doses, ranitidine's effects upon doxorubicin plasma pharmacokinetics are similar to those previously seen with cimetidine. These changes did not appear to alter drug detoxification and are not related to microsomal inhibition of doxorubicin detoxification. Low doses of ranitidine do not alter doxorubicin plasma pharmacokinetics or toxicity in rabbits.

Aminopyrine↗

PubMed2006

Saturable absorptive transport of the hydrophilic organic cation ranitidine in Caco-2 cells: role of pH-dependent organic cation uptake system and P-glycoprotein.

PURPOSE: The purpose of this work was to investigate the involvement of carrier-mediated apical (AP) uptake and efflux mechanisms in the absorptive intestinal transport of the hydrophilic cationic drug ranitidine in Caco-2 cells. METHODS: Absorptive transport and AP uptake of ranitidine were determined in Caco-2 cells as a function of concentration. Permeability of ranitidine in the absorptive and secretory directions was assessed in the absence or presence of the P-glycoprotein (P-gp) inhibitor, GW918. Characterization of the uptake mechanism was performed with respect to inhibitor specificity, pH, energy, membrane potential, and Na+ dependence. Efflux from preloaded monolayers was evaluated over a range of concentrations and in the absence or presence of high extracellular ranitidine concentrations. RESULTS: Saturable absorptive transport and AP uptake of ranitidine were observed with Km values of 0.27 and 0.45 mM, respectively. The ranitidine absorptive permeability increased and secretory permeability decreased upon inhibition of P-gp. AP ranitidine uptake was inhibited in a concentration-dependent fashion by a diverse set of organic cations including tetraethylammonium, 1-methyl-4-phenylpyridinium, famotidine, and quinidine. AP ranitidine uptake was pH and membrane potential dependent and reduced under conditions that deplete metabolic energy. Efflux of [3H]ranitidine across the basolateral membrane was neither saturable as a function of concentration nor trans stimulated by unlabeled ranitidine. CONCLUSIONS: Saturable absorptive transport of ranitidine in Caco-2 cells is partially mediated via a pH-dependent uptake transporter for organic cations and is subject to attenuation by P-gp. Inhibition and driving force studies suggest the uptake carrier exhibits similar properties to cloned human organic cation transporters. The results also imply ranitidine transport is not solely restricted to the paracellular space.

2,4-Dinitrophenol↗

PubMed1996

Ranitidine bismuth citrate plus clarithromycin is effective for healing duodenal ulcers, eradicating H. pylori and reducing ulcer recurrence. RBC H. pylori Study Group.

AIM: To compare the efficacy of the coadministration of ranitidine bismuth citrate plus the antibiotic clarithromycin, with ranitidine bismuth citrate alone or clarithromycin alone for the healing of duodenal ulcers, eradication of H. pylori and the reduction of ulcer recurrence. METHODS: This two-phase, randomized, double-blind, placebo-controlled, multicentre study consisted of a 4-week treatment phase followed by a 24-week post-treatment observation phase. Patients with an active duodenal ulcer were treated with either ranitidine bismuth citrate 400 mg b.d. for 4 weeks plus clarithromycin 500 mg t.d.s. for the first 2 weeks; ranitidine bismuth citrate 400 mg b.d. for 4 weeks plus placebo t.d.s. for first 2 weeks; placebo b.d. for 4 weeks plus clarithromycin 500 mg t.d.s. for the first 2 weeks; or placebo b.d. for 4 weeks plus placebo t.d.s. for the first 2 weeks. RESULTS: Ulcer healing rates after 4 weeks of treatment were highest with ranitidine bismuth citrate plus clarithromycin (82%) followed by ranitidine bismuth citrate alone (74%; P = 0.373), clarithromycin alone (73%; P = 0.33) and placebo (52%; P = 0.007). Ranitidine bismuth citrate plus clarithromycin provided significantly better ulcer symptom relief compared with clarithromycin alone or placebo (P < 0.05). The coadministration of ranitidine bismuth citrate plus clarithromycin resulted in significantly higher H. pylori eradication rates 4 weeks post-treatment (82%) than did treatment with either ranitidine bismuth citrate alone (0%; P < 0.001), clarithromycin alone (36%; P = 0.008) or placebo (0%; P < 0.001). Ulcer recurrence rates 24 weeks post-treatment were lower following treatment with ranitidine bismuth citrate plus clarithromycin (21%) compared with ranitidine bismuth citrate alone (86%; P < 0.001), clarithromycin alone (40%; P = 0.062) or placebo (88%; P = 0.006). All treatments were well tolerated. CONCLUSIONS: The coadministration of ranitidine bismuth citrate plus clarithromycin is a simple, well-tolerated and effective treatment for active H. pylori-associated duodenal ulcer disease. This treatment regimen effectively heals duodenal ulcers, provides effective symptom relief, eradicates H. pylori infection and reduces the rate of ulcer recurrence. The eradication of H. pylori infection in patients with recently healed duodenal ulcers is associated with a significant reduction in the rate of ulcer recurrence.

Adolescent↗

PubMed2006

Ranitidine in acute high-dose organophosphate exposure in rats: effect of the time-point of administration and comparison with pyridostigmine.

Weak and reversible inhibitors of cholinesterase, when co-administered in large doses, can act in a protective manner against more potent inhibitors such as organophosphates. The clinically widely used histamine type 2 (H2) receptor blocker ranitidine is among H2 blockers the most potent inhibitor of acetylcholinesterase but roughly three to four orders of magnitude less potent than paraoxon (an irreversible organophosphate esterase inhibitor) or pyridostigmine (a reversible carbamate esterase inhibitor). We have previously shown that in vitro ranitidine confers some protection against inhibition of cholinesterases by paraoxon and that in vivo it both increases the number of rats surviving an acute paraoxon exposure and also protects to some degree the cholinesterases from organophosphate inhibition. The purpose of the study was to compare in a prospective non-blinded study, in a rat model of acute high-dose paraoxon exposure, ranitidine with pyridostigmine either administered simultaneously or 30 min. before exposure. There were 36 rats in each of the 5 groups. All substances were applied intraperitoneally. Additional analysis included data from a similar experiment carried out in 2005, in which 54 rats were exposed to paraoxon only (G1) and 54 to paraoxon+ranitidine simultaneously (G2). All groups (except controls; G6 & G7) received 1 micro Mol paraoxon (approximately LD75); groups 2-5 received in addition to paraoxon: G2: 50 micro Mol ranitidine within 1 min. of paraoxon, G3: 1 micro Mol pyridostigmine within 1 min. of paraoxon, G4: 50 micro Mol ranitidine 30 min. before paraoxon, G5: 1 micro Mol pyridostigmine 30 min. before paraoxon. Groups 6 & 7 received only ranitidine and pyridostigmine respectively, group G1 received only paraoxon. Mortality was recorded at 30 min., 1, 2, 3, 4, 24 and 48 hr. Mortality data were compared using Kaplan-Meier plots and logrank tests. No Bonferroni correction for multiple comparisons was applied and an alpha < or = 0.05 was considered significant. All statistical analysis was performed by using SPSS 12.0 statistical software (SPSS Inc., Chicago, IL, USA). Simultaneous administration of ranitidine or pyridostigmine with paraoxon does not significantly affect mortality. Pretreatment (30 min. before) with both ranitidine or pyridostigmine statistically and significantly reduced mortality. When administered before paraoxon, pyridostigmine is statistically significantly superior to ranitidine. Both ranitidine and pyridostigmine are protective against acute paraoxon toxicity provided they are administered before paraoxon. Pyridostigmine results are statistically significantly superior to ranitidine (< or =0.05).

Animals↗

PubMed1993

Effect of ranitidine bismuth citrate on postprandial plasma gastrin and pepsinogens.

Ranitidine bismuth citrate was compared with an equipotent dose of ranitidine, to determine whether the former, by an anti-Helicobacter pylori activity, would counteract the rise of gastrin resulting from ranitidine's gastric acid antisecretory activity. Twenty four men with duodenal ulcers were studied before and on the 8th day of dosing with either ranitidine bismuth citrate 800 mg twice daily or ranitidine 300 mg twice daily (double blind, randomised, parallel groups). Fasting and postprandial plasma gastrin and plasma pepsinogen I and II concentrations were measured, and a 13C-urea breath test was performed before and on the 8th day of dosing. The 13C-urea breath tests were positive in 21 patients before dosing and remained positive in nine of nine of the ranitidine dosed patients, whereas only two of 12 patients treated with ranitidine bismuth citrate remained positive. The expected rise in meal stimulated plasma gastrin with ranitidine was seen in the 12 patients who received ranitidine but, despite suppression of H pylori urease activity in 10 of 12 patients taking ranitidine bismuth citrate, there was no attenuation of the meal stimulated gastrin rise. There was no significant difference in the mean derived (4 hour) plasma pepsinogen I and II concentrations after dosing with ranitidine or ranitidine bismuth citrate.

Adult↗

PubMedDate not supplied

Prevention of relapse in reflux esophagitis: a placebo controlled study of ranitidine 150 mg bid and 300 mg bid.

OBJECTIVE: To compare the efficacy and safety of long term use of ranitidine 150 mg bid, 300 mg bid and placebo in prevention of endoscopic and symptomatic relapse of reflux esophagitis in an international, double-blind, placebo controlled, parallel group study. PATIENTS AND METHODS: A total of 279 patients at least 18 years old from hospital out-patient departments with healed esophagitis (grade 0) with no or mild symptoms entered the study. Patients were randomly allocated to receive ranitidine 150 mg, 300 mg placebo twice daily for 48 weeks. Patients returned for symptom assessments at eight-week intervals and for re-endoscopy every 16 weeks. RESULTS: Both ranitidine regimens were significantly more effective than placebo in preventing endoscopic and symptomatic relapse of reflux esphagitis (p = 0.003 for ranitidine 150 mg bid; P < 0.001 for ranitidine 300 mg bid). No statistically significant differences were observed in relapse rates between the two ranitidine regiments. The percentage of patients with endoscopic relapse (grade 2) after 48 weeks were 60%, 37% and 27% for placebo, ranitidine 150 mg bid and ranitidine 300 mg bid, respectively (P = 0.002 for ranitidine 150 mg bid versus placebo; P < 0.001 for ranitidine 300 mg bid versus placebo). Ranitidine was well tolerated. CONCLUSIONS: Ranitidine 150 mg bid and 300 mg bid are safe and effective treatments in the prevention of reflux esophagitis relapse.

Adolescent↗

PubMed1996

Omeprazole versus ranitidine or ranitidine/metoclopramide in poorly responsive symptomatic gastroesophageal reflux disease.

OBJECTIVES: To evaluate complete symptom resolution, mucosal healing, and tolerability of omeprazole, ranitidine, or ranitidine/metoclopramide in patients with poorly responsive, symptomatic gastroesophageal reflux disease (GERD). METHODS: Adults with persistent symptomatic GERD after ranitidine treatment were stratified by esophagitis grade and randomized to omeprazole 20 mg once daily, ranitidine HCI 150 mg twice daily, or ranitidine HCI 150 mg twice daily plus metoclopramide HCI 10 mg four times daily. Endoscopies were conducted at baseline and at wk 4 and 8. Patients assessed overall symptom improvement at wk 4 and 8 and evaluated daytime and nighttime heartburn, dysphagia, and acid regurgitation daily. RESULTS: After 1 wk, 13% of patients receiving omeprazole (N = 100) had complete resolution of all GERD symptoms versus 1% and 3% of patients receiving ranitidine (N = 97) or ranitidine/metoclopramide (N = 93), respectively (p < 0.001). More patients receiving omeprazole had complete symptom resolution at wk 4 (33%) and at the end of the study (64%; both p < 0.001) than patients receiving ranitidine (8% and 28%, respectively) or ranitidine/metoclopramide (7% and 29%, respectively). Regardless of baseline esophagitis grade, more patients receiving omeprazole had complete symptom resolution. At wk 8, more than 91% of patients with grade 0 or 1 esophagitis at baseline were still healed irrespective of treatment. At wk 8, 80% of patients with esophagitis grade 2 or higher at entry were healed with omeprazole (p < 0.001 vs ranitidine [40%] and ranitidine/metoclopramide [46%]). Thirty-four percent of patients reported an adverse event. Significantly more patients receiving combination treatment reported an adverse event than patients treated with single agents. CONCLUSIONS: In patients with persistent GERD symptoms after ranitidine, omeprazole (20 mg daily for up to 8 wk) provides faster and more complete resolution of common GERD symptoms than continued ranitidine (300 mg daily) alone or in combination with metoclopramide (40 mg daily). Omeprazole provides significantly higher rates of endoscopic healing than ranitidine alone or with metoclopramide. Omeprazole and ranitidine are generally well tolerated. The addition of metoclopramide to ranitidine significantly increases adverse events.

Dopamine Antagonists↗

PubMedDate not supplied

Ranitidine-acetaminophen interaction: effects on acetaminophen-induced hepatotoxicity in Fischer 344 rats.

Cimetidine has been shown to protect against acetaminophen-mediated hepatotoxicity in both rats and mice. In contrast to cimetidine, ranitidine recently has been determined to potentiate the hepatotoxic action of acetaminophen in Fischer 344 rats. The present studies were designed to characterize this ranitidine-acetaminophen interaction. Acetaminophen administration (750 mg per kg, p.o.) to F344 rats produced maximal hepatic necrosis, 24 hr after treatment, as assessed by SGPT activity and histopathology. Ranitidine pretreatment 30 min prior to acetaminophen treatment increased the toxicity but did not alter its course. Ranitidine administration (50 mg per kg) enhanced acetaminophen hepatotoxicity throughout the toxic dose range of acetaminophen (600 to 1,000 mg per kg) and potentiation of acetaminophen hepatotoxicity by ranitidine was dose-dependent. Maximal increases were observed at 50 mg per kg ranitidine whereas, doses of ranitidine greater than 100 mg per kg inhibited acetaminophen toxicity. SGPT data were corroborated by histopathologic evaluation. Ranitidine was not hepatotoxic when administered alone (500 mg per kg), or following glutathione depletion, or after induction of hepatic mixed-function oxidase activity. The results obtained in these studies support the suggestion that, at high doses (greater than 100 mg per kg), ranitidine reduces acetaminophen hepatotoxicity by reducing metabolic activation, while at lower doses ranitidine potentiates acetaminophen hepatotoxicity. Inhibition by ranitidine of acetaminophen conjugation is proposed as a possible mechanism of this potentiation.

Acetaminophen↗

PubMed1989

Determination of ranitidine in plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic method has been developed for the determination of ranitidine in plasma. Ranitidine was extracted with acetonitrile by adding it to the plasma and then salting it out with potassium carbonate. The chromatographic column was 5-microns ODS silica, the mobile phase being acetonitrile-7 mM triethylammonium ion in phosphoric acid (pH 3.00) (30:70, v/v). The ranitidine peak was monitored at a wavelength of 315 nm, the retention time for ranitidine being 4.6 min. A limit of detection of 3 ng ml-1 was obtained for a 100-microliters injection of ranitidine. The method was found to be reproducible with a relative standard deviation (RSD) between 0.8-5.3% (n = 5) over the concentration range 25-80 ng ml-1 in plasma. The ranitidine concentration was determined in 18 different patients' plasmas. Ranitidine and its metabolites ranitidine S-oxide, ranitidine N-oxide and desmethyl-ranitidine, were also studied for chromatographic resolution from each other. It was shown that a group of common drugs did not interfere with ranitidine determination.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

Effect of preanesthetic intramuscular ranitidine on gastric acidity and volume in children.

STUDY OBJECTIVE: To evaluate the effects of preanesthetic administration of intramuscular (IM) ranitidine on pH and volume of gastric contents in children. DESIGN: Three randomized treatment groups. SETTING: Central operating rooms at a university hospital. PATIENTS: Forty children age 1 to 10 years undergoing a variety of elective surgical procedures requiring general anesthesia with endotracheal intubation. INTERVENTIONS: IM ranitidine 1 mg/kg (n = 15) or 2 mg/kg (n = 15) was administered 2 hours prior to induction of anesthesia. Ten patients without ranitidine served as the control group. An orogastric tube was inserted into each patient. MEASUREMENTS AND MAIN RESULTS: Gastric fluid pH and volume were measured every hour in the three groups. Plasma ranitidine concentrations were measured in ten patients of the ranitidine-treated groups. The mean volume of gastric fluid at induction of anesthesia was significantly lower in the ranitidine-treated patients (2.4 ml for ranitidine 1 mg/kg, 3.2 ml for ranitidine 2 mg/kg) than in the controls (8.6 ml; p less than 0.05). The mean pH values at induction of anesthesia were significantly higher in the ranitidine-treated patients (4.6 for 1 mg/kg, 6.7 for 2 mg/kg) than in the controls (2.1; p less than 0.05). Dose-dependent plasma ranitidine concentrations were obtained. CONCLUSIONS: Preanesthetic IM ranitidine 1 to 2 mg/kg resulted in a higher pH and lower volume of gastric fluid at the time of induction and in a higher pH during 3 hours of anesthesia. This therapy may be a useful adjunct to premedication for children who have a greater than normal risk of pulmonary aspiration during anesthesia.

Child↗

PubMed2002

The effect of ranitidine on the pharmacokinetics of rosiglitazone in healthy adult male volunteers.

BACKGROUND: Rosiglitazone is an insulin-sensitizing oral agent in the thiazolidinedione class used to treat patients with type 2 diabetes mellitus. It binds to peroxisome proliferator-activated receptor gamma in liver, muscle, and adipose tissue. Ranitidine, a histamine2-receptor antagonist, may be prescribed for patients with type 2 diabetes and esophageal symptoms such as heartburn. By raising gastrointestinal pH levels, ranitidine may affect the bioavailability of coadministered drugs. OBJECTIVES: This article presents the absolute bioavailability of rosiglitazone, as well as the effects of ranitidine on the pharmacokinetics of rosiglitazone. METHODS: Healthy men were enrolled in a randomized, open-label, 4-period, period-balanced crossover study of rosiglitazone and ranitidine. All individuals received each of 4 regimens successively, separated by a 4-day washout period: a single IV dose of rosiglitazone 2 mg administered alone over 1 hour; a single IV dose of rosiglitazone 2 mg administered over 1 hour on the fourth day of treatment with oral ranitidine 150 mg given every 12 hours; a single oral dose of rosiglitazone 4 mg alone; and a single oral dose of rosiglitazone 4 mg on the fourth day of treatment with oral ranitidine 150 mg given every 12 hours. The primary end point was dose-normalized area under the plasma concentration-time curve from time 0 to infinity (AUC(0-infinity)). Maximum observed plasma concentration (Cmax), the time at which Cmax occurred (Tmax), plasma clearance (CL), steady-state volume of distribution (Vss), and terminal elimination half-life (t 1/2) were also assessed. RESULTS: Twelve individuals were enrolled. The absolute bioavailability of rosiglitazone was 99%. For AUC(0-infinity), the point estimate and the associated 95% CI for the ratio of ranitidine + IV rosiglitazone to IV rosiglitazone alone was 1.02 (range, 0.88-1.20). With oral rosiglitazone, the AUC(0-infinity) point estimate (95% CI) for the ratio of ranitidine + rosiglitazone to rosiglitazone alone was 0.99 (range, 0.85-1.16). Cmax, Tmax, t 1/2, Vss and CL of rosiglitazone, whether administered orally or intravenously, were unaffected by ranitidine. Oral and IV rosiglitazone were associated with a favorable safety profile and were well tolerated with or without concurrent ranitidine treatment. CONCLUSIONS: In this study of 12 healthy adult male volunteers, the absolute bioavailability of rosiglitazone was 99%, and the oral and IV single-dose pharmacokinetics of rosiglitazone were unaltered by concurrent treatment with ranitidine.

Administration, Oral↗

PubMed1995

Regional gastrointestinal absorption of ranitidine in the rat.

PURPOSE: Ranitidine absorption from isolated segments of rat small intestine (duodenum, midgut, and terminal ileum) was investigated to examine the influence of pH and 50% bile, and to determine if ranitidine is absorbed preferentially from a specific region. METHODS: Ranitidine (50 mg/kg) was administered into each segment in pH 5 or pH 7 buffer, or in 50% bile. Venous blood was collected at various times for 40 min from the right jugular vein. RESULTS: When ranitidine was administered in pH 7 buffer or in 50% bile, Cmax and AUC0-40 were significantly greater after administration into the terminal ileum compared to the duodenum and midgut. AUC0-40 was significantly greater when ranitidine was administered in pH 5 buffer or in 50% bile into the duodenum compared to the midgut. Cmax was significantly different between administration into the duodenum and midgut only when ranitidine was administered in 50% bile. Ranitidine administration in pH 5 buffer significantly decreased AUC0-40 and Cmax after administration into the midgut, and AUC0-40 after administration into the terminal ileum compared to administration with pH 7 buffer or in 50% bile. Bile had no significant effect on AUC0-40 after ranitidine administration into the duodenum and midgut compared to administration in pH 7 buffer. However, bile significantly increased AUC0-40 and Cmax after ranitidine administration into the terminal ileum compared to administration with pH 7 and pH 5 buffer. CONCLUSIONS: Results suggest that ranitidine is absorbed from the entire small intestine. However, the terminal ileum is the optimal site of gastrointestinal absorption. Furthermore, bile enhances ranitidine absorption from the terminal ileum.

Animals↗

PubMed1999

Lansoprazole is superior to ranitidine as maintenance treatment for the prevention of duodenal ulcer relapse.

AIM: To compare lansoprazole 30 mg once daily, lansoprazole 15 mg once daily and ranitidine 150 mg once nightly in the prevention of duodenal ulcer relapse in patients whose duodenal ulcers had been previously healed with lansoprazole 30 mg once daily or ranitidine 300 mg nightly. METHODS: A double-blind, parallel group, randomized multicentre study conducted in 33 centres in the UK, Eire, Sweden and Australia. Two hundred and nineteen patients with a duodenal ulcer were randomized to receive lansoprazole 30 mg and 217 to receive ranitidine 300 mg for 8 weeks. Patients were then re-randomized to receive lansoprazole 30 mg (122 patients), lansoprazole 15 mg (121 patients) or ranitidine 150 mg (116 patients) for 12 months. All patients had an endoscopically-proven duodenal ulcer at baseline and were considered suitable for long-term maintenance therapy to prevent relapse. RESULTS: Significantly more patients were healed on lansoprazole (98%) compared to ranitidine (89%) (P < 0.001, Fisher's exact test). Lansoprazole provided more rapid symptom relief than ranitidine. Lansoprazole 30 mg and lansoprazole 15 mg increased the probability of not relapsing in comparison to ranitidine (P = 0.001 and 0.06, respectively, life-table analysis). Relapse rates over the 12 months were lower in the lansoprazole treatment groups (lansoprazole 30 mg, 5%; lansoprazole 15 mg, 12%; and ranitidine, 21%; lansoprazole 30 mg vs. ranitidine 150 mg, P = 0.002). Symptoms were well controlled in both groups during the maintenance phase. All treatments were well tolerated with no major differences seen in adverse event profiles between treatment groups. CONCLUSIONS: Both doses of lansoprazole (30 mg and 15 mg) were superior to ranitidine 150 mg in the prevention of duodenal ulcer relapse. Lansoprazole was superior to ranitidine in terms of symptom control and duodenal ulcer healing. Both treatments were well tolerated.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1991

Lack of ranitidine effects on cyclophosphamide bone marrow toxicity or metabolism: a placebo-controlled clinical trial.

We previously reported that cimetidine but not ranitidine significantly enhances cyclophosphamide-induced bone marrow toxic effects and the appearance of cyclophosphamide alkylating species in a murine leukemia mouse model, and we advised caution in the use of cimetidine with microsomally metabolized anticancer drugs. Both drugs have been used for the treatment of gastric complications of chemotherapy. Using a randomized, double-blind, crossover study design, we have now evaluated the potential interaction of ranitidine with cyclophosphamide in seven cancer patients, who received two courses of cyclophosphamide, one with ranitidine and one with placebo. Four patients received ranitidine in the first course, and three received placebo. Ranitidine or placebo was started 3 days before a single dose of cyclophosphamide and given for 17 consecutive days. Ranitidine or placebo was given orally (300 mg/d), and cyclophosphamide (600 mg/m2) was given intravenously with [3H]cyclophosphamide (1000 muCi). Cyclophosphamide treatment was repeated at 4 weeks plus or minus 4 days. Blood samples were collected at intervals from 5 minutes to 24 hours after cyclophosphamide treatment and analyzed by thin-layer chromatography and radioassay for the drug and its metabolites. On days 0, 7, 14, and 21 after cyclophosphamide administration, complete blood cell counts, white blood cell differential counts, platelet counts, and SMA-17 were determined. The differences in mean nadir white blood cell counts, granulocyte counts, hemoglobin levels, and hematocrit values during ranitidine versus placebo treatment were not statistically significant. In a statistical but not a clinical sense, mean nadir platelet counts were significantly lower with ranitidine. There was a statistically significant increase in area under the curve for drug concentration in plasma x time (AUC) with ranitidine as well as a statistically significant decrease in the total-body clearance rate of the cyclophosphamide molecule. However, the effect on AUC for the major oncolytic metabolites 4-hydroxycyclophosphamide and phosphoramide mustard was not statistically significant. The lack of toxicologic or metabolic interaction between ranitidine and cyclophosphamide suggests that ranitidine can be used safely with cyclophosphamide.

Adult↗

PubMedDate not supplied

Nonprescription doses of ranitidine are effective in the relief of episodic heartburn.

BACKGROUND: Many Americans have heartburn or related symptoms monthly and >20% experience heartburn at least once per day. Although many self-treat episodic heartburn with nonprescription antacids, newer treatments that decrease gastric volume and increase the pH of refluxed material are proving effective and popular in relieving heartburn. AIM: To evaluate the safety and efficacy of low-dose regimens of ranitidine for the relief of heartburn. METHODS: Adults with at least a 3-month history of heartburn were eligible for this randomized, double-blind, parallel group, multicenter dose-ranging study. Following a 1-week, open-label run-in phase to document baseline heartburn frequency, subjects were randomly assigned to receive treatment with one tablet of either ranitidine, 75 mg (n = 537); ranitidine, 25 mg (n = 539); or placebo (n = 544), to be taken as needed up to four times daily for 2 weeks for the relief of heartburn. RESULTS: The ranitidine 75-mg regimen was statistically (P < 0.05) and clinically (as defined a priori as > or =10% improvement) more effective than placebo in relieving episodic heartburn and in reducing antacid consumption. Ranitidine, 25 mg, was also statistically superior (P < 0.05) to placebo in providing heartburn relief. In addition, both regimens were superior to placebo in providing heartburn relief within 30 to 45 minutes of dosing. Ranitidine continued to be as effective over placebo in the treatment of the last heartburn episode as in the treatment of the first heartburn episode. Ranitidine was also equally effective over placebo in the treatment of mild, moderate, and severe episodes of heartburn. Ranitidine, 75 mg, was statistically superior to placebo for the relief of nocturnal heartburn episodes, whereas ranitidine, 25 mg, was not. All treatments were well tolerated and adverse events occurred no more frequently with the ranitidine regimens than with placebo. CONCLUSIONS: Low-dose ranitidine provides prompt and lasting relief of heartburn and has a safety profile comparable to that of placebo.

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