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T J Humphries

Publications and source records attributed to T J Humphries.

At least 37 records · Page 2Linked to original sources
PubMed1998

An ascending single-dose safety and tolerance study of an oral formulation of rabeprazole (E3810).

BACKGROUND: Proton pump inhibitors such as omeprazole produce a long-lasting inhibition of gastric acid secretion associated with significant increases in plasma gastrin. Rabeprazole (E3810) is a new substituted benzimidazole H+,K+ ATPase inhibitor. It acts as an irreversible, non-competitive inhibitor of the H+,K+ ATPase and preliminary studies demonstrate that rabeprazole produces a potent and long-lasting inhibition of gastric acid secretion and a low level of hypergastrinaemia. AIM: This randomized, double-blind, placebo-controlled study was performed to further examine the effects of different single doses of rabeprazole on gastric acid secretion and serum gastrin. METHODS: In this study, four groups of 10 healthy, non-smoking Helicobacter pylori-negative men (mean age 22.5 +/- 3.9 years) received single oral doses of 10, 20, 30 and 40 mg of rabeprazole. Two of the 10 volunteers in each group received placebo as part of the double-blind study design. All volunteers who entered into the study had a normal gastric acid secretory capacity as evaluated by pentagastrin challenge. Prior to administration of the first dose of test drug, volunteers underwent an inpatient 24-h measurement of baseline intragastric pH. One week later, volunteers received the test drug and again underwent an inpatient 24-h measurement of intragastric pH. During both periods, plasma samples were collected at specified intervals over 48 h and were sent for analysis of rabeprazole and gastrin levels. RESULTS: Administration of rabeprazole resulted in a dose-dependent increase in the duration and extent of intragastric pH elevation. The response among all volunteers receiving drug was significantly different from placebo, with greater acid inhibition occurring in the 30 and 40 mg groups. In addition, there was also a dose-related increase in plasma gastrin. The pharmacokinetics of rabeprazole were similar to those of other proton pump inhibitors with a t1/2 of between 0.7 and 1.0 h. There were no clinically significant effects on patient laboratory tests or serious adverse events. CONCLUSIONS: The results of this study suggest that rabeprazole is as potent as omeprazole and lansoprazole in inhibiting gastric acid secretion.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Comparison of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of active gastric ulcer--a European multicentre study. The European Rabeprazole Study Group.

BACKGROUND: Rabeprazole sodium is the newest member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing active, benign gastric ulcers. METHODS: In this randomized, double-blind, multicentre study, conducted at 25 European sites, rabeprazole and omeprazole were compared in patients with active gastric ulcers. Two hundred and twenty-seven patients with active benign gastric ulcer were randomized to receive either rabeprazole 20 mg (n = 113) or omeprazole 20 mg (n = 114) once daily for 3 or 6 weeks, with healing monitored by endoscopy. RESULTS: After 3 weeks, complete healing (ITT analysis) was documented in 58% of patients given rabeprazole and 61% in patients given omeprazole (N.S.). After 6 weeks the healing rates were identical in both groups at 91%. Rabeprazole-treated patients had numerically greater symptom relief at all 12 points of comparison. The differences significantly favoured rabeprazole at week 3 for daytime pain improvement (P = 0.023) and at week 6 for pain frequency (P = 0.006) and complete resolution of night pain (P = 0.022). Both drugs were well-tolerated over the 6-week treatment course. Mean changes from baseline to end-point in fasting serum gastrin were comparable. No significant differences in laboratory parameters were seen. CONCLUSION: In this study, rabeprazole produced healing rates comparable to omeprazole at weeks 3 and 6, but provided more consistent and occasionally significantly superior symptom improvement. Both treatments were well-tolerated.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Effects of oral rabeprazole on oesophageal and gastric pH in patients with gastro-oesophageal reflux disease.

BACKGROUND: This study examined the dose-response effects of the new proton-pump inhibitor rabeprazole on oesophageal and gastric pH in patients with gastro-oesophageal reflux disease. METHODS: This study had a single-centre, double-blind, randomized, two-way crossover design. Twenty patients were treated for two 7-day periods separated by a 7-10-day washout period. Patients were randomly assigned to receive either 20 mg of rabeprazole once daily during the first treatment period and 40 mg once daily during the second treatment period, or 40 mg during the first treatment period and 20 mg during the second treatment period. The primary efficacy variable was oesophageal acid exposure determined by 24-hour ambulatory pH monitoring. Acid-reflux time was defined as the percentage of time over 24 h that oesophageal pH was < 4. A dosage was considered effective if reflux time was reduced to < 6%, a number which has been our internal laboratory reference. RESULTS: Both rabeprazole 20 mg and 40 mg, given once daily, normalized reflux time, with decreases of 79% and 92% in acid exposure by day 7. Both dosages also decreased the mean total number of reflux episodes and the number of episodes lasting > 5 min, with no significant differences between dosages for any reflux parameter. Mean gastric pH increased with 20 mg from 1.86 at baseline to 3.71 on day 1 and 4.17 on day 7. Rabeprazole 40 mg once daily increased gastric pH from 2.01 to 4.37 on day 1, and to 4.65 on day 7. Safety analyses revealed no significant acute side-effects for either dosage. CONCLUSIONS: Pathological oesophageal acid exposure was normalized with both 20 mg and 40 mg dosages of rabeprazole, and the effects of these two doses did not differ. Rabeprazole was well-tolerated in this short-term study.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1991

Clinical implications of drug interactions with the cytochrome P-450 enzyme system associated with omeprazole.

Interactions with the hepatic cytochrome P-450 microsomal enzyme system, as evidenced by statistically significant changes in pharmacokinetic parameters, have been described with some H2-receptor antagonists. Omeprazole is the first of a new class of antisecretory agents inhibiting gastric secretion by blocking hydrogen potassium ATPase. Omeprazole contains a benzimidazole moiety and thus has the potential to interact with the cytochrome P-450 enzyme group. In vitro, in vivo and human clinical studies have assessed whether such an interaction occurs, and the potential clinical consequences, in patients receiving omeprazole therapy. In vitro studies have demonstrated that omeprazole influences O-deethylation and N-demethylation in liver microsomes and the clearance and elimination half-life of antipyrine in isolated perfused liver preparations. Overall, the studies reviewed suggest that omeprazole has a differential affinity toward specific cytochrome P-450 isozymes. In vivo animal studies have demonstrated that omeprazole prolongs pentobarbital sleep times and half-life and decreases [14C]-aminopyrine elimination. Human clinical studies have not demonstrated the "all or none" effect of omeprazole on cytochrome P-450-mediated drug interactions, as is seen with cimetidine. These studies confirm in vitro findings that omeprazole is a differential inhibitor of drug metabolism: interactions have been demonstrated with the model drugs aminopyrine and antipyrine, and the therapeutic drugs diazepam, phenytoin, and warfarin but not with theophylline or propranolol. Although caution should be exercised when initiating omeprazole therapy in patients taking concomitant diazepam, warfarin, and phenytoin, clinically significant drug interactions appear unlikely.

Aminopyrine↗
PubMed1991

Famotidine (20 mg) b.d. relieves gastrooesophageal reflux symptoms in patients without erosive oesophagitis. Famotidine/GERD Investigation Group.

Previous clinical trials have evaluated a large number of symptomatic individuals with heartburn. Most studies have documented the need for multiple daily dosing with H2-antagonists to achieve clinical and statistical efficacy for symptom relief. The purpose of this study was to compare the safety profile and efficacy of famotidine oral dosing regimens, 40 mg nocte and 20 mg b.d. with placebo in the relief of symptoms in patients suffering from frequent heartburn found to have endoscopically normal oesophageal mucosa or mild non-erosive oesophagitis. Famotidine (20 mg) b.d. reduced and eventually completely relieved gastro-oesophageal reflux disease symptoms in most patients during the 6-week trial. Global assessment of improvement at 2 and 6 weeks indicated significantly greater improvement with a b.d. treatment regimen than with either a 40 mg nocte or placebo treatment. No statistically significant differences between famotidine and placebo in the number of patients who experienced clinical adverse experiences were noted and no serious adverse events attributable to famotidine occurred. Based upon these findings, patients with gastro-oesophageal reflux symptoms experience good relief of their complaints with twice daily famotidine in standard doses.

Administration, Oral↗
PubMed1991

Effect of different doses of omeprazole on 24-hour oesophageal acid exposure in patients with gastro-oesophageal reflux.

To define the optimum doses of omeprazole appropriate for acute and long-term therapy of patients with gastro-oesophageal reflux disease, 24-h oesophageal pH was measured in 12 patients with symptomatic reflux and an abnormal 24-h oesophageal acid exposure time (greater than 6%) in a randomized, double-blind, four-way crossover study comparing the effects of omeprazole 10, 20, or 40 mg/day and placebo. Total reflux time over 24 hours, number of reflux episodes per hour, and the number of reflux episodes lasting greater than 5 minutes were measured by ambulatory 24-h oesophageal pH monitoring. All doses of omeprazole were superior to placebo in decreasing gastro-oesophageal reflux as measured by each index. With placebo, oesophageal acid exposure was 16.3% of the 24 hours, 10 mg omeprazole/day reduced that to 6.3%, 20 mg/day lowered acid exposure to 0.9%, and 40 mg/day to 0.6%. Thus only the 20 and 40 mg doses reduced acid exposure to within the normal range. Similar results were obtained with the other indices of reflux. These data suggest that a rational dose regimen for reflux oesophagitis is 20 mg/day, a regimen that has proved effective in clinical trials. The present study indicates that 24-hour oesophageal pH monitoring is a practical approach to the determination of drug dosage in patients with gastro-oesophageal reflux.

Adult↗
PubMed1991

Famotidine relieves symptoms of gastroesophageal reflux disease and heals erosions and ulcerations. Results of a multicenter, placebo-controlled, dose-ranging study. USA Merck Gastroesophageal Reflux Disease Study Group.

We conducted a double-blind, placebo-controlled, multicenter trial comparing the efficacy of famotidine 40 mg administered at bedtime (HS), 20 mg given twice daily (BID), and placebo to relieve heartburn and to heal endoscopically documented esophageal erosions or ulcerations. A total of 338 patients were randomized: 135 to receive famotidine 40 mg HS, 137 to receive famotidine 20 mg BID, and 66 to receive placebo. In the group given famotidine 20 mg BID, there was a significantly greater proportion of patients with complete relief of daytime heartburn, and both famotidine groups demonstrated statistically significant advantages over placebo in global scores or by successful outcome. Antacid consumption was significantly reduced in the group given famotidine 20 mg BID as compared with placebo. Both famotidine regimens resulted in a significantly greater proportion of patients with complete endoscopic healing than placebo, with the BID dosing being numerically superior to the 40-mg HS dose.

Adult↗
PubMed1991

The establishment and validation of the mobile immunization team concept at a clinic level.

Faced with unacceptably low and declining overall immunization compliance, as well as specific flu immunization compliance, the Executive Committee of a 32-person Air National Guard clinic asked the nursing service to devise a method of correcting these deficiencies as rapidly as possible and maintaining immunization compliance at a rate of 90% or better of the total patient population of approximately 1,100 full-time and Guard personnel for whom the clinic was responsible. The concept of a mobile immunization team was devised and validated over a 2-year interval. In order to successfully develop and implement this concept, command emphasis and a high level of cooperation from both clinic personnel and the Unit Commanders involved was requested and received. The make-up of the team, risk management, the timing and place of team visits, and record keeping were among the problems addressed and resolved. The mobile immunization team concept was a success, achieving excellent overall immunization compliance and outstanding compliance with the flu immunization program over a 2-year period.

Health Promotion↗
PubMed1989

Report of an Air National Guard clinic's experience with screening at-risk individuals before initial physical fitness testing.

AFR 35-11, dated 10 April 1985, included standards for physical fitness performance tests with the option of a 1.5-mile run or a 3-mile walk. Since that time, ANG units have begun initial physical fitness testing of all personnel. This program brought with it new responsibilities for ANG medical units including the screening of individuals in whom health problems might indicate that they are at risk in taking the physical fitness test (PFT). The 111th TAC Clinic used a questionnaire, screened by physicians utilizing a predetermined grid of responses to designate individuals cleared for the run or walk test or as at risk. Of 823 individuals screened, 91 (11%) were designated at risk. These individuals are being further evaluated and 31 (29%) have been subsequently cleared to date. Physical testing of cleared individuals was accomplished, and both running and walking courses were carefully monitored by ambulance crews. Four casualties came to medical attention (blisters, severe fatigue, dizziness, and indigestion). The patient with severe fatigue was a patient on medical hold, S/P myocardial infarction, who had not been medically cleared to participate. The patient with light-headedness was found to have newly diagnosed hypertension. In view of the relatively small number of casualties incurred during this initial PFT, it is felt that the screening process employing a questionnaire evaluated by medical personnel is an appropriate method of minimizing risk.

Female↗
PubMed1988

Dose--response effect of famotidine on patterns of gastro-oesophageal reflux.

The present study attempts to assess the alteration in patterns of gastro-oesophageal reflux as assessed by 24-h oesophageal pH monitoring by varying degrees of H2-receptor blockade with famotidine. Subjects were 12 patients with complaints of daily heartburn who demonstrated at least 6% of acid mucosal contact time by 24-h ambulatory oesophageal pH monitoring. All subjects had a positive Bernstein test, and nine of the 12 subjects had erosive oesophagitis. The study was conducted as a double-blind crossover design utilizing 40 mg nocte, 20 mg b.d., and 40 mg b.d. and placebo treatments. Results indicated that all treatments significantly reduced the 24-h percentage acid contact time (P less than 0.05) compared to placebo. The two b.d. treatment regimens also significantly (P less than 0.05) reduced the number of episodes lasting longer than 5 min. Only the b.d. regimens successfully lowered the percentage of upright acid exposure. All treatments significantly (P less than 0.01) reduced the percentage of supine acid contact time, as well as the number of episodes lasting more than 5 min. It is concluded that gastro-oesophageal reflux disease may well require a b.d. dosing regimen with famotidine in order to achieve optimal mucosal healing and day time symptom control.

Adult↗
PubMed1987

Effects of long-term medical treatment with cimetidine and bethanechol in patients with esophagitis and Barrett's esophagus.

To evaluate long-term medical therapy in patients with Barrett's esophagus, six patients were studied before and after long-term therapy with cimetidine for a mean period of 11.7 months. Some patients also received bethanechol. All had severe symptoms of gastroesophageal reflux resistant to intensive antacid therapy, specialized columnar epithelium by biopsy, and endoscopic evidence of severe inflammation. Esophageal manometry documented a hypotensive lower esophageal sphincter in three patients and low peristaltic amplitude in the distal esophagus in four. Treatment was begun with cimetidine, 300 mg orally four times daily. If symptoms did not totally abate, bethanechol, 25 mg orally four times daily, was added. Cimetidine completely relieved or dramatically reduced symptoms in all patients. Adding bethanechol produced further symptomatic improvement in three of four patients. After initial dilatation in the two patients with strictures, there was no recurrence. Endoscopic evidence of inflammation resolved completely in four patients and was markedly improved in two. Treatment with both drugs was well tolerated by all patients. The abnormally placed squamo-columnar junction did not regress during follow-up.

Adult↗
PubMed1987

Review of an extensive worldwide study of a new H2-receptor antagonist, famotidine, as compared to ranitidine in the treatment of acute duodenal ulcer.

The efficacy and safety of famotidine, a new potent H2-receptor antagonist, has been studied in 1,031 patients by 68 investigators in 19 countries in a worldwide dose-ranging multicenter comparative study. Three doses of famotidine (40 mg h.s., 20 mg b.i.d., 40 mg b.i.d.) were compared to ranitidine 150 mg b.i.d. There were no significant differences between the groups in baseline characteristics, including duodenal ulcer size. Efficacy parameters included daytime and nocturnal symptom relief and duodenal ulcer healing, documented by endoscopy, and defined as complete re-epithelialization of the ulcer crater. Significant reductions from baseline for day and night pain, beginning during the first 24 h period, were found in all four treatment groups (p less than 0.01). There was little difference among the four treatment groups with respect to the percentage of patients healed after 4 and 8 weeks of treatment. Healing rates for the three famotidine groups (40 mg h.s., 20 mg b.i.d., 40 mg b.i.d.) were 88, 92 and 92%, respectively, after 8 weeks of treatment as compared to 91% for the ranitidine group. The occurrence and type of adverse clinical experiences reported was similar for each of the four treatment groups. The most common adverse experiences were headache and diarrhea. The results of this study demonstrate that an h.s. dose of famotidine is equivalent to both b.i.d. famotidine and b.i.d. ranitidine in duodenal ulcer healing and pain relief. In view of possible increased patient compliance with a simplified dosage regimen, famotidine 40 mg h.s. is recommended in the acute treatment of duodenal ulcer.

Acute Disease↗
PubMed1987

Famotidine: a notable lack of drug interactions.

Cimetidine, an H2-receptor antagonist, has been shown to inhibit the oxidative metabolism of several drugs by interacting with the hepatic cytochrome P450 system, which is involved in phase-I oxidative drug metabolism. Ranitidine, another H2-receptor antagonist, has been shown to have an extremely low level of interaction with the cytochrome P450 system. The potential of famotidine, a new H2-receptor antagonist with a guanylthiazole ring structure, to interact with the cytochrome P450 system has been extensively evaluated. Many of the studies used cimetidine and/or ranitidine as active controls. In vitro studies investigated the potential effects of famotidine coadministration on aminopyrine and diazepam demethylase activity, disturbances of P450 spectra, and effects on the metabolism of specific substrates such as deethylation of 7-ethoxycoumarin and demethylation of benzphetamine. Famotidine and ranitidine showed negligible interaction with the cytochrome P450 reactions studied, in contrast to the rather marked interaction demonstrated with cimetidine. Several in vivo animal studies investigated the effect of famotidine on hexobarbital sleeping time; plasma concentrations of diazepam, warfarin, and propranolol; antipyrine elimination kinetics; and warfarin prothrombin complex activity. Famotidine and ranitidine demonstrated either no evidence or minimal evidence of interaction with cytochrome P450 functions, in direct contrast to marked interactions produced by cimetidine. Human studies investigated the potential of an interaction with the coadministration of famotidine and aminopyrine, antipyrine, diazepam, theophylline, phenytoin, and warfarin. Coadministration of famotidine had no effect on the pharmacokinetic variables of theophylline, diazepam, desmethyldiazepam, and phenytoin and no effect on the half-life of antipyrine and aminopyrine or on the prothrombin time ratios associated with warfarin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗