Document Detail


The Influence of Dirithromycin on the Pharmacokinetics of Cyclosporine in Healthy Subjects and in Renal Transplant Patients.
MedLine Citation:
PMID:  11850697     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The effect of a standard regimen of the investigational macrolide antibiotic, dirithromycin, on the single-dose kinetics of orally administered cyclosporine (CSA) was investigated in healthy young males and on the steady-state disposition kinetics of cyclosporine in a panel of renal transplant patients. Eight male volunteers participated after giving informed consent. CSA was administered in three single doses (15 mg kg(minus sign1) p.o. each) in each of three phases: (1) prior to a 14-day regimen of dirithromycin; (2) at the end of a 14-day regimen of dirithromycin (500 mg p.o. qAM); and (3) 2 weeks after the last dose of a 14-day regimen of dirithromycin. Pharmacokinetic parameters of CSA were estimated, and the differences among treatments were assessed by analysis of variation. No significant differences among treatment (phase) means were detected (p < 0.05). We conclude that a typical 14-day regimen of dirithromycin failed to alter the disposition kinetics of CSA when taken orally healthy young adult males. The effect of a standard regimen of dirithromycin on the steady-state disposition kinetics of orally administered CSA was investigated in a panel of 15 stable renal transplant patients. Pharmacokinetic parameters for CSA were evaluated prior to, during, and 2 weeks after discontinuing a 14-day (500 mg day(minus sign1)) oral regimen of dirithromycin. Dirithromycin elicited small but significant changes in the following parameters: C(av) was increased by 16% during dirithromycin treatment, and the changes in normalized C(av) were comparable. Likewise, C(SS,min) and normalized C(SS,min) were increased by 19% and 20%, respectively, during dirithromycin treatment. CSA oral clearance, CL/F(SS), decreased by 17% during dirithromycin treatment. C(SS,max) and normalized C(SS,max) were increased by 13% and 17%, respectively, during dirithromycin treatment but were not significantly different from those either before or after dirithromycin. The magnitude of the pharmacokinetic changes for CSA during dirithromycin treatment (<15% in normal subjects and 15--20% in renal transplant patients) when considered in the context of the therapeutic range of cyclosporine concentrations was relatively small, and not likely to warrant special attention to the dosing of CSA in such patients beyond routine whole-blood CSA and serum creatinine monitoring.
Authors:
Kenneth Bachmann; Timothy J. Sullivan; James H. Reese; Luis Jauregui; Kristen Miller; Mary Scott; Gregory D. Sides; Ronald Shapiro
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Publication Detail:
Type:  JOURNAL ARTICLE    
Journal Detail:
Title:  American journal of therapeutics     Volume:  2     ISSN:  1536-3686     ISO Abbreviation:  Am J Ther     Publication Date:  1995 Jul 
Date Detail:
Created Date:  2002-Feb-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9441347     Medline TA:  Am J Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  490-498     Citation Subset:  -    
Affiliation:
Center for Applied Pharmacology of The University of Toledo, USA.
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