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A Pharmacokinetic Interaction Between Clarithromycin and Sirolimus in Kidney Transplant Recipient

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Bacterial infection is a frequent event in renal transplant recipients and often requires the use of antimicrobial agents. In this paper it is reported an evidence of pharmacokinetic interaction between clarithromycin and sirolimus in a kidney transplanted woman, suffering from pulmonary infection sustained by a bacterial pathogen, in particular Hemophilus Influenzae. In the present case report, the concomitant administration of clarithromycin and sirolimus determined impressive increase of sirolimus trough blood concentrations from 6.2 up to 54 ng/mL and this increase was associated with an acute impairment of renal function, almost completely reversed upon both drugs discontinuation.

This drug-drug interaction is due to a likely inhibition of activity of both cytochrome P450 3A4 and P-glycoprotein. Although this interaction could be predicted, it represents the first reported clinical evidence.



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Keywords: Sirolimus; clarithromycin; nephrotoxicity; pharmacokinetics; therapeutic drug monitoring

Document Type: Research Article

Affiliations: Department of Clinical and Experimental Medicine, Section of Hepatology in Internal Medicine, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy.

Publication date: May 1, 2007

More about this publication?
  • Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.
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