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https://hdl.handle.net/2440/33969
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Type: | Journal article |
Title: | Multiple Interactions of Cimetidine and Probenecid with Valaciclovir and Its Metabolite Acyclovir |
Author: | De Bony, F. Tod, M. Bidault, R. On, N. Posner, J. Rolan, P. |
Citation: | Antimicrobial Agents and Chemotherapy, 2002; 46(2):458-463 |
Publisher: | Amer Soc Microbiology |
Issue Date: | 2002 |
ISSN: | 0066-4804 1098-6596 |
Statement of Responsibility: | F. De Bony, M. Tod, R. Bidault, N. T. On, J. Posner, and P. Rolan |
Abstract: | The effects of probenecid and cimetidine on the pharmacokinetics of valaciclovir and its metabolite acyclovir have been investigated. Twelve healthy male volunteers participated in this open single-dose study with a four-way-crossover randomized and balanced design. At the first of four administrations, volunteers in four groups received 1 g of valaciclovir alone, valaciclovir with 1 g of probenecid, valaciclovir with 800 mg of cimetidine, or valaciclovir with a combination of probenecid and cimetidine. At three subsequent administrations, drug regimens were alternated among groups so that each group received each regimen. Probenecid and cimetidine increased the mean maximum concentrations in serum (Cmax) of valaciclovir by 23 and 53% and the areas under the concentration-time curves (AUC) for valaciclovir by 22 and 73%, respectively; probenecid and cimetidine also increased the mean acyclovir Cmax by 22 and 8% and its AUC by 48 and 27%, respectively. The combination had a greater effect than either drug alone. Their effects may be due to competitive inhibition of membrane transport of valaciclovir and acyclovir in the liver and kidney. Neither cimetidine nor probenecid affected the absorption of valaciclovir. Both probe drugs reduced the rate of valaciclovir metabolism but not its extent. These pharmacokinetic modifications did not affect the tolerability of valaciclovir. |
Keywords: | Humans Probenecid Cimetidine Acyclovir Valine Area Under Curve Cross-Over Studies Drug Interactions Drug Tolerance Adult Male Valacyclovir |
DOI: | 10.1128/AAC.46.2.458-463.2002 |
Published version: | http://dx.doi.org/10.1128/aac.46.2.458-463.2002 |
Appears in Collections: | Aurora harvest 6 Pharmacology publications |
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