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PubMed1993

Clarithromycin is bactericidal against strains of Mycobacterium leprae resistant and susceptible to dapsone and rifampin.

The anti-Mycobacterium leprae activity of clarithromycin when administered alone and in combination with rifampin and dapsone in the diet was determined using the kinetic method of drug evaluation in mice. Clarithromycin when administered at a concentration of 0.1% (w/w) in the diet completely prevented growth of 2 pan-susceptible, 3 dapsone-resistant, 2 rifampin-resistant, and 2 rifampin and dapsone double resistant strains of M. leprae. A 0.03% (w/w) concentration also completely prevented growth of M. leprae in all mice infected with 2 of 7 strains tested, but in only some of the mice infected with the remaining 5 strains. No antagonistic drug interactions were observed between clarithromycin and dapsone or rifampin. The addition of clarithromycin to the currently recommended multidrug regimen should improve the rate of killing of M. leprae and help to prevent the growth of dapsone-resistant and rifampin-resistant strains.

Administration, Oral↗
PubMedDate not supplied

A preliminary study of clarithromycin versus doxycycline in the treatment of nongonococcal urethritis and mucopurulent cervicitis.

In a comparison of drug safety and efficacy, 40 adult outpatients with clinical signs and symptoms of nongonococcal urethritis or mucopurulent cervicitis were treated with either clarithromycin 250 mg or doxycycline 100 mg twice/day for 7 days. Clinical and laboratory evaluations were repeated during, at the end, and 3 weeks after the completion of therapy. Isolation and susceptibility tests of Chlamydia and Mycoplasma isolates were performed at each visit. All but one patient who received doxycycline were clinically cured or improved at the end of treatment. Two (10%) patients who received clarithromycin and three (15%) who received doxycycline had clinical relapses of the infection. All isolates of Chlamydia trachomatis were eradicated and did not recur in both groups. Doxycycline was more effective than clarithromycin in eradicating Ureaplasma urealyticum (p < 0.01). Both groups reported a high frequency of minor adverse effects, but no patient discontinued therapy. Overall, clarithromycin was clinically safe and effective treatment in patients with nongonococcal urethritis and mucopurulent cervicitis.

Adolescent↗
PubMed1996

Clinical ergotism with lingual ischemia induced by clarithromycin-ergotamine interaction.

The macrolide class of antibiotics, including erythromycin and troleandomycin, is associated with clinically significant adverse drug interactions. This results from macrolide inhibition of cytochrome P-450 metabolism of numerous xenobiotics, resulting in elevated serum drug levels and clinical intoxication. Animal studies, however, suggest that clarithromycin, the newest approved macrolide antibiotic, has has less potential for adverse drug reactions. We describe a patient who, on her fifth day of clarithromycin therapy, developed clinical ergotism (i.e., hypertension, lingual ischemia, and peripheral cyanosis) several hours after administration of her usual 2-mg dose of ergotamine tartrate. To our knowledge, this is the first report of clinical ergotism precipitated by clarithromycin-ergotamine interaction and suggests that, like other macrolide antibiotics, ergot preparations should be avoided in patients who are taking clarithromycin.

Clarithromycin↗
PubMedDate not supplied

The role of clarithromycin in the prophylaxis of disseminated Mycobacterium avium-intracellulare infection in patients with AIDS.

Clarithromycin is a first-line agent in the treatment of disseminated disease due to Mycobacterium avium-intracellulare (dMAC) in patients with the acquired immunodeficiency syndrome, and its role in dMAC prophylaxis is nearing definition. Fifteen abstracts described clinical outcomes when clarithromycin was given in various dosages as monoprophylaxis or in combination with other agents. Patients totaled 1063, the majority of whom had CD4+ counts of 100 cells/mm3 or below. In one study, MAC disease occurred in 4.5% of 343 clarithromycin-treated patients compared with 12.6% of 341 receiving placebo (p < 0.001). The remaining studies combined to report only two positive blood cultures, one positive sputum culture, and one positive culture of unidentified origin during their respective study periods. Gastrointestinal intolerance caused discontinuation of therapy in 21 (2.9%) of 722 patients receiving clarithromycin. Clinical evaluations show that the drug decreases the risk of dMAC, prolongs survival, and is well tolerated. Controlled clinical trials continue.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Interaction between midazolam and clarithromycin: comparison with azithromycin.

A comparative pharmacokinetic and pharmacodynamic investigation was carried out on the interaction between the hypnotic midazolam and 2 different macrolide-type antibiotics, clarithromycin and azithromycin. In an open randomized crossover study of 3 phases 12 healthy volunteers received either clarithromycin (250 mg twice a day for 5 days), azithromycin (500 mg once a day for 3 days) or no pretreatment. On the last day of antibiotic treatment they ingested 15 mg midazolam. Plasma samples were collected for midazolam analysis up to 24 h and pharmacodynamic performance measured by a series of tests up to 12 h. Pretreatment with clarithromycin caused large and statistically significant changes in both the pharmacokinetic and pharmacodynamic parameters of midazolam compared to control. For example, the AUC was increased from 248.84-888.75 hng/ml (factor of 3.57, p < 0.0001) and the mean duration of sleep increased from 135.4 min to 281.3 min (p < 0.05). No statistically significant effect was found with azithromycin in any test. It is concluded that a drug interaction exists between midazolam and clarithromycin which could be of clinical importance. No such effect is present with azithromycin.

Adult↗
PubMed1996

Significant increase in eradication rates of Helicobacter pylori infection with two consecutive dual therapies (omeprazole and amoxycillin or omeprazole and clarithromycin). A randomized study in 450 Spanish patients.

Helicobacter pylori infection is associated with peptic ulcer disease and chronic gastritis, and eradication of the microorganism markedly reduces the recurrence of peptic ulcer. However, a major problem is the choice of a treatment that is effective, has high eradication rate, and is well tolerated by patients. We evaluated the eradication of H. pylori infection in patients with chronic gastritis (CG), duodenal ulcer (DU), and gastric ulcer (GU) after two dual therapies (omeprazole with either amoxycillin or clarithromycin). Of 450 patients initially included in the study, 207 had CG, 187 DU and 56 GU, and all presented with H. pylori infection. Diagnosis was made from endoscope examination, biopsy samples, rapid urease test and 13C-urea breath test (UBT). H. pylori infection was considered to be present when two of the tests had positive results. All patients were randomized to one of two regimens: (A) omeprazole (20 mg b.i.d.) plus amoxycillin (750 mg t.i.d.) or (B) omeprazole (40 mg b.i.d.) plus clarithromycin (500 mg t.i.d.). The duration of each of the regimens was 2 weeks. Fifty-eight patients who showed H. pylori infection after the first treatment (27 with CG, 24 with DU, and 7 with GU) were allocated to a second therapy. H. pylori eradication was assessed by UBT, 6 weeks after the end of the therapies; positive values were those higher than 5 delta units. A second consecutive dual therapy of omeprazole plus an antibiotic (amoxycillin or clarithromycin) not used in the first therapy improved on the eradication rates obtained with the first regimen. The overall eradication rates were also higher, but no significant differences were found between amoxycillin and clarithromycin. The best results were obtained in those patients with GU.

Adult↗
PubMed1997

Clarithromycin in the combination therapy for the eradication of Helicobacter pylori in peptic ulcer disease.

BACKGROUND: Clarithromycin is a new macrolide antibiotic which is known to be highly effective in eradicating Helicobacter pylori (H. pylori). In Chinese, the role of clarithromycin for H. pylori is still unclear. METHODS: Between January 1995 and February 1996, 75 patients with active H. pylori-positive duodenal ulcer were enrolled in this study. Three groups were randomized to have (1) 2 x 150 mg nizatidine twice daily, 2 x 250 mg amoxicillin four times daily, and 2 x 250 mg clarithromycin three times daily for two weeks (niz-amox-clar group, N = 25); or (2) 20 mg omeprazole twice daily plus 2 x 250 mg clarithromycin three times daily for two weeks (ome-clar group, N = 25); or (3) 300 mg bismuth subsalicylate four times daily, and 2 x 250 mg amoxicillin four times daily, 250 mg metronidazole four times daily for two weeks (triple therapy group, N = 25). All the patients received H2 receptor antagonist (150 mg nizatidine or ranitidine, or 400 mg cimetidine, twice daily) for the consecutive six weeks. RESULTS: The eradication rate of H. pylori eight weeks after the entry of study was 80%(20/25) in the niz-amox-clar group, 76%(19/25) in the ome-clar group, 88%(22/25) in the triple therapy group (p < 0.05 among the three groups). The ulcer healing rates eight weeks after the entry of study for the niz-amox-clar, the ome-amox, and the triple therapy groups were 84%(21/25), 80%(20/25), and 80%(20/25), respectively (p < 0.05 among the three groups). The number of patients experiencing adverse effects in the niz-amox-clar group, the ome-clar group, and the triple therapy group were 10(40%), 7(28%), and 4(16%), respectively (p > 0.05 among the three groups). CONCLUSIONS: Both nizatidine/amoxicillin/clarithromycin and omeprazole/clarithromycin regimens can achieve good eradication rates and may provide an effective alternative anti-H. pylori treatment in duodenal ulcer diseases.

Adult↗
PubMed1997

Bismuth subsalicylate instead of metronidazole with lansoprazole and clarithromycin for Helicobacter pylori infection: a randomized trial.

OBJECTIVE: We evaluated the efficacy of lansoprazole, clarithromycin, and metronidazole (LCM) administered twice daily for 7 days. Because there is growing concern about the development of metronidazole-resistant H. pylori (HP) strains, we also tested a novel regimen consisting of lansoprazole, clarithromycin, and bismuth subsalicylate (LCB). METHODS: Patients with active HP infection and peptic ulcer, a history of peptic ulcer, or nonulcer dyspepsia were randomized to either lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d., and metronidazole 500 mg b.i.d. or lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d., and bismuth subsalicylate 524 mg b.i.d. (LCB) for 7 days. Compliance and side effects were recorded by using a diary. RESULTS: "Per protocol" eradication with LCM was achieved in 41 of 47 (87%). By using "intention to treat" analysis, LCM eradicated HP infection in 43 of 53 patients (81%). By using "per protocol" analysis, LCB eradicated HP infection in 40 of 47 patients (85%). On an "intention to treat" basis, LCB led to HP eradication in 42 of 52 (81%). The most common significant side effects observed with LCM were altered taste (39%) and abdominal pain (19%). With LCB, the most common significant side effects were altered taste (23%) and dark stools (23%). CONCLUSIONS: LCB for 7 days was as effective in eradicating HP infection as a 7-day course of LCM. Further studies evaluating the role of bismuth compounds in proton-pump inhibitor based triple therapy are warranted. Such therapy may have particular importance in areas where high metronidazole resistance is a concern.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Ranitidine bismuth citrate plus clarithromycin for the eradication of H. pylori.

Reported observed intention-to-treat eradication rates for ranitidine bismuth citrate plus clarithromycin for 14 days range from 70-86% in studies from the USA and 82-96% in multinational studies carried out primarily in Europe. Two double-blind head-to-head comparisons with omeprazole plus clarithromycin or amoxycillin have shown that ranitidine bismuth citrate plus clarithromycin gives considerably higher eradication rates than the omeprazole based regimens. Ongoing studies will define the efficacy of shorter duration dual therapies and provide further data on two antibiotics with ranitidine bismuth citrate. The possibility that ranitidine bismuth citrate may help in the eradication of resistant organisms and even in the prevention of primary resistance requires further work to expand the preliminary in vitro observations. In the meantime, it can be concluded that ranitidine bismuth citrate, when used in conjunction with clarithromycin for 14 days, is an effective therapy for the eradication of H. pylori.

Anti-Bacterial Agents↗
PubMed1998

[new one-week triple therapies with metronidazole for the eradication of Helicobacter pylori: clarithromycin or amoxycillin as the second antibiotic].

BACKGROUND: To compare the efficacy of two "new" one-week triple therapies (with omeprazole, metronidazole and clarithromycin or amoxycillin) for the eradication of Helicobacter pylori and healing duodenal ulcer. METHODS: Randomised therapeutic trial. Eighty-eight consecutive duodenal ulcer patients with H. pylori infection were studied. At endoscopy, biopsies from both gastric antrum and body were obtained for histologic study (H&E). Two different therapies were administered for one week: omeprazole (O) (20 mg b.i.d.) and metronidazole (M) (500 mg b.i.d.) associated with clarithromycin (C) (500 mg b.i.d.) (group OMC, n = 44) or amoxycillin (A) (1 g b.i.d.) (group OMA, n = 44). Endoscopy with biopsies was repeated one month after completing therapy, and a 13C-urea breath test was also performed. Compliance was evaluated by tablet count. Analysis of data: multiple logistic regression, intention-to-treat. Eradication was defined as the absence of H. pylori by all diagnostic methods. RESULTS: Mean age (standard deviation) was 45(14) years, 75% males. Distribution of variables was similar in both therapeutic groups. Forty-two patients in each group completed the protocol. Eradication was achieved in 90.5% (95% CI = 78-96%) in group OMC and in 57% (42-71%) in group OMA (p < 0.001). In the multivariate analysis the type of therapy was the only variable which influenced on H. pylori eradication (OR = 7.1; CI = 2.2-24; p = 0.001). Ulcer healing was demonstrated in 88% (75-95%) of patients in group OMC and in 71% (56-83%) in group OMA (p = 0.1). Ulcer healing was higher when eradication was achieved (90%; 80-95%) than in H. pylori-positive patients (50%; 31-69%) (p < 0.001). Eradication of H. pylori was the only variable which influenced on ulcer healing (OR = 9.3; CI = 2.8-31; p < 0.001). CONCLUSION: The "new" triple therapy with omeprazole, metronidazole and clarithromycin (administered in a twice-a-day basis and only for one week) had an excellent efficacy for the eradication of H. pylori, significantly higher than that obtained with amoxycillin instead of clarithromycin. Both therapies achieved a high ulcer healing rate when H. pylori was eradicated, even with omeprazole administered only for one week.

Adult↗
PubMed2004

[Real-time PCR assay for rapid detection of clarithromycin-resistant helicobacter pylori in gastric biopsy specimens].

The main cause for failure of Helicobacter pylori eradication therapy is resistance to clarithromycin which is due to point mutations. The use of real-time PCR allows the detection of these mutations directly on biopsy specimens within a few hours. In our routine laboratory, we compared LightCycler PCR to conventional detection and susceptibility testing of H. pylori by culture. PCR showed a positive result for H. pylori in 74 specimens. PCR was confirmed by culture in 69 specimens. In five specimens which were positive by PCR but negative on culture the (13)C urea breath test confirmed the PCR results. Sensitivity and specificity of our LightCycler assay for the detection of H. pylori in biopsy specimens were both 100 %. In 26 out of 68 specimens conventional susceptibility testing yielded resistance to clarithromycin. Corresponding point mutations were found in 24 of these specimens. Compared to culture, PCR gave a false-resistant, respectively, a false sensitive result in one specimen each. In another specimen, culture yielded a resistant strain whereas PCR detected both a resistant mutant and the wild-type strain. From two other specimens clarithromycin-sensitive strains were cultured but both a wild-type strain and a mutant were detected by PCR. Sensitivity and specificity of LightCycler PCR for resistance to clarithromycin were 96.2 % and 97.6 %, respectively. This assay had an accuracy comparable to culture and could be performed within 3 hours, allowing it to be used before the administration of H. pylori eradication therapy.

Adult↗
PubMed1998

Eradication of Helicobacter pylori by a 1-week course of famotidine, amoxicillin and clarithromycin.

OBJECTIVES: The combination of a proton pump inhibitor (PPI) such as omeprazole with amoxicillin and clarithromycin constitutes one of the most effective treatments for the eradication of Helicobacter pylori. Nevertheless, the mechanisms of interaction between these drugs remain unclear. It has been shown that minimal inhibitory concentration values of both antibiotics are considerably lower at neutral pH levels than in an acid environment. Further, omeprazole possesses bacteriostatic activity. To evaluate the significance of these mechanisms we replaced omeprazole with famotidine, a drug which only suppresses acid production, but has no intrinsic antimicrobial activity. METHODS: We evaluated the efficacy of a 1-week course of famotidine 80 mg b.i.d., amoxicillin 1000 mg b.i.d. and clarithromycin 500 mg b.i.d. in a pilot study (20 patients), and then confirmed our results in a larger replication study (87 patients). A total of 107 patients with H. pylori-associated duodenal ulcer (n = 54), gastric ulcer (n = 14) or non-ulcer dyspepsia (n = 39) were included. Endoscopy was performed at baseline and 4-6 weeks after discontinuation of treatment. H. pylori status was assessed by the urease test and histology. RESULTS: H. pylori was successfully eradicated in 94 of 104 patients who completed the study (90.4%; CI 95%, 83.0-95.3%). By intention-to-treat analysis, the eradication rate was 87.9% (CI 95%, 80.1-93.4%). Ulcer healing was observed in 98.1% of duodenal ulcers and 92.9% of gastric ulcers (based on per-protocol analysis). Mild side effects that did not require termination of treatment were reported by seven patients (6.7%). CONCLUSION: A 1-week course of famotidine, amoxicillin and clarithromycin is a highly effective, simple and safe eradication regimen. Our data indicate that acid suppression is the crucial mechanism by which the activity of amoxicillin and clarithromycin against H. pylori is enhanced, whereas additional antimicrobial activity or other specific effects of PPIs seem to be less important.

Adult↗
PubMed1999

The effect of carbon dioxide on susceptibility testing of azithromycin, clarithromycin and roxithromycin against clinical isolates of Streptococcus pneumoniae and Streptococcus pyogenes by broth microdilution and the Etest: Artemis Project-first-phase study.

OBJECTIVE: To evaluate the effect of carbon dioxide on the susceptibility testing, using broth microdilution and the Etest (AB Biodisk, Solna, Sweden), of azithromycin, clarithromycin and roxithromycin against Streptococcus pneumoniae and Streptococcus pyogenes. METHODS: Fresh clinical isolates collected from 36 hospital laboratories in 12 countries were evaluated using the Etest in the presence of carbon dioxide. The isolates were retested under ambient conditions (absence of carbon dioxide) using broth microdilution and/or the Etest. RESULTS: Carbon dioxide falsely elevated azithromycin, clarithromycin and roxithromycin MIC90S for S. pneumoniae, determined by the Etest, approximately 12-fold. Also, the azithromycin MIC90 for S. pyogenes was increased fourfold; the effect was less marked for clarithromycin and roxithromycin. When isolates were retested in the absence of carbon dioxide, using the Etest or microdilution, susceptibilities to azithromycin were comparable to those to clarithromycin (S. pneumoniae, 93.4% versus 91.3%; S. pyogenes, 96.4% versus 95.8%). Both organisms were less susceptible to roxithromycin (S. pneumoniae, 71.3%; S. pyogenes, 85.7%). An internal standard control, consisting of 50 isolates each of S. pneumoniae, S. pyogenes and Haemophilus influenzae, confirmed that azithromycin susceptibility testing resulted in falsely elevated MICs. CONCLUSIONS: Carbon dioxide falsely elevated azithromycin MICs for S. pneumoniae and S. pyogenes, with an apparent reduction in susceptibility. When the in vitro activity of azithromycin and other macrolides against S. pneumoniae and S. pyogenes is being evaluated, awareness of the pH effect is essential.

Journal Article↗
PubMed2003

Bismuth-based quadruple therapy using a single capsule of bismuth biskalcitrate, metronidazole, and tetracycline given with omeprazole versus omeprazole, amoxicillin, and clarithromycin for eradication of Helicobacter pylori in duodenal ulcer patients: a prospective, randomized, multicenter, North American trial.

OBJECTIVES: This multicenter, randomized, active-controlled trial assessed efficacy of bismuth-based quadruple therapy with omeprazole, bismuth biskalcitrate, metronidazole, and tetracycline (OBMT) using a single-triple capsule of BMT compared with triple therapy with omeprazole, amoxicillin, and clarithromycin (OAC) in treatment of patients with Helicobacter pylori infection and duodenal ulcers. METHODS: Patients with active duodenal ulcer or diagnosed within the past 5 yr and with infection documented by (13)C-urea breath test plus histology or culture were randomly assigned to 10-day course of OBMT using a single-triple capsule containing bismuth biskalcitrate 140 mg, metronidazole 125 mg, and tetracycline 125 mg given as three capsules q.i.d. with omeprazole 20 mg b.i.d., or a 10-day course of OAC, omeprazole 20 mg plus amoxicillin 1 g plus clarithromycin 500 mg, all b.i.d. Eradication was confirmed by two negative urea breath tests at >1 month and >2 months after therapy. RESULTS: One hundred thirty-eight patients received OBMT and 137 OAC. Modified intent-to-treat eradication rates were 87.7% for OBMT and 83.2% for OAC (95% CI = -3.9%-12.8%; p = 0.29). OBMT eradicated 91.7% metronidazole-sensitive and 80.4% metronidazole-resistant strains (p = 0.06). OAC eradicated 92.1% clarithromycin sensitive and 21.4% clarithromycin-resistant strains (p < 0.001). Adverse events occurred in 58.5% of OBMT patients and 59.0% of OAC patients. CONCLUSIONS: OBMT regimen using the single-triple capsule is as efficacious and well-tolerated as the widely used OAC regimen for H. pylori eradication. This OBMT therapy largely overcomes H. pylori metronidazole resistance, present in 40% of patients in this study.

Administration, Oral↗
PubMed2002

Fulminant hepatitis and fatal toxic epidermal necrolysis (Lyell disease) coincident with clarithromycin administration in an alcoholic patient receiving disulfiram therapy.

Disulfiram is widely used in the treatment of chronic alcoholism. Adverse drug reactions with fatal outcome following disulfiram therapy are infrequent, and hepatic failure accounts for most of them. Since disulfiram is a cytochrome P450 (CYP450) enzyme system inhibitor, numerous interactions with several drugs metabolized in the liver have been reported. Like disulfiram, clarithromycin inhibits a CYP450 isoenzyme, but, despite its widespread use for the treatment of respiratory tract infections, no interactions with disulfiram have been described as yet. We report a case of fatal toxic epidermal necrolysis (Lyell disease) and fulminant hepatitis shortly after starting treatment with clarithromycin in a patient who was receiving disulfiram. This is the first case of such a severe dermatosis in a patient receiving either disulfiram or clarithromycin therapy. The temporal relationship between drug administration and clinical symptoms in this case suggests a probable interaction between the 2 drugs.

Alcohol Deterrents↗
PubMed2001

Determination of clarithromycin in human plasma by HPLC with electrochemical detection: validation and application in pharmacokinetic study.

A rapid, specific, precise and accurate HPLC method with electrochemical detection was developed and validated for the determination of clarithromycin in human plasma. After addition of the internal standard, the analytes were extracted from plasma under alkaline conditions with ethyl acetate:hexane 1:1. The inter-run precision of the method was less than 4.7%, the inter-run accuracy was better than 97.3% and the recovery of clarithromycin and roxithromycin (internal standard) were better than 82.5% and 86.2%, respectively. The method was found to be suitable for the quantitation of clarithromycin in bioequivalence and pharmacokinetic studies.

Anti-Bacterial Agents↗
PubMed2006

Liquid chromatographic-electrospray tandem mass spectrometric determination of clarithromycin in human plasma.

A rapid, sensitive and specific LC-MS-MS method has been developed for the determination of clarithromycin (CLA) in human plasma using roxithromycin (ROX) as the internal standard. Samples were prepared via liquid-liquid extraction with methyl tert-butyl ether (MTBE) and chromatographed on a Supelco RP(18) (4.6 x 50 mm, 3 microm particle size) column with a mobile phase consisting of acetonitrile:methanol:60 mM (pH 3.5) ammonium acetate buffer (32.5:32.5:35) at a constant flow rate of 0.8 mL/min. The run time was 3 min with retention times of approximately 1.65 and 1.70 min for CLA and ROX, respectively. Detection was performed on a PE Sciex API 365 mass spectrometer equipped with a turboionspray ionization source in multiple reaction monitoring (MRM) mode. The MRM pairs were m/z 748.5 --> m/z 158.2 for CLA and m/z 837.7 --> m/z 679.3 for ROX, respectively, with dwell times of 200 ms for each transition. The validated calibration curve range was 5.00-5000 ng/mL, based on 0.100 mL plasma sample volume with signal-to-noise ratio (S/N) greater than 60 for CLA at the lower limit of quantification level (5.00 ng/mL). The correlation coefficients (r(2)) of the calibration curves were better than or equal to 0.996. The inter-day (n = 18) precision and accuracy of the quality control (QC) samples were less than 3.58% RSD (relative standard deviation) and -10.8% bias, respectively. The intra-day (n = 6) precision and accuracy of the quality control samples were less than 5.0 and 12.6%, respectively. There was no significant deviation from the nominal values after a 10-fold dilution of high concentration QC samples using blank matrix. The QC samples were stable when left on the bench for 24 h or after three freeze-thaw cycles. The processed samples were also stable in HPLC autosampler at 10C for over 72 h. No matrix ionization suppression was observed when extracted blank matrix or reconstitution solvent was injected onto the system with post-column infusion of clarithromycin and roxithromycin. No carryover was observed when an extracted blank plasma sample was injected immediately after a 5000 ng/mL ULOQ (the upper limit of quantification) standard. The mean recovery was 81.5 and 78.3%, respectively, for clarithromycin and internal standard.

Chromatography, High Pressure Liquid↗
PubMed1993

Effect of moderate or severe hepatic impairment on clarithromycin pharmacokinetics.

The pharmacokinetic and safety profiles of clarithromycin (C) and its 14-hydroxy-clarithromycin (HC) metabolite were determined after a multiple-dose oral clarithromycin regimen (250 mg twice daily for five doses) in six healthy subjects and seven patients with moderate or severe hepatic impairment (Pugh grades B and C). Plasma and urine C and HC concentrations were determined using high-performance liquid chromatography. Hepatic impairment resulted in increased harmonic mean C terminal disposition half-life and mean +/- SD C renal clearance (CLR) compared with normal volunteers (5.0 vs. 3.3 hr and 170 +/- 69 vs. 111 +/- 17 mL/min, respectively). Hepatic impairment also resulted in decreased metabolite peak plasma concentration and area under the plasma concentration-versus-time curve and decreased metabolite/parent concentration ratios compared with normal volunteers. These data suggest that 14-hydroxylation of C was reduced by moderate to severe hepatic impairment. No adverse events were noted in either study group and there were no study-related clinically significant changes in laboratory parameters. The decrease in C metabolic clearance appears to be partially offset by an increase in C CLR, resulting in comparable steady-state concentrations of parent drug. In those indications in which the metabolite may be a necessary element of the antimicrobial activity of C, it would seem prudent to be cautious in using C in patients with moderate to severe hepatic impairment due to reduced production of HC. Otherwise, no dosage adjustment for C appears necessary for subjects with moderate or severe hepatic impairment provided that renal function is not impaired.

Chromatography, High Pressure Liquid↗