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CYP3A5 genotype has a dose-dependent effect on ABT-773 plasma levels by KATZ, D is a Medicine article available to read on EtoBox.

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## Background: The metabolizing enzyme cytochrome p450 (cyp) 3a5 is polymorphically expressed as a result of genetic variants that do not encode functional protein. because of overlapping substrate specificity with cyp3a4 and the multidrug efflux pump p-glycoprotein, the importance of cyp3a5 genetic polymorphism for pharmacokinetics is controversial. ## Objective: Our objective was to determine whether genetic polymorphisms in cyp3a5 or mdr-1 (which encodes p-glycoprotein) influence the drug levels of abt-773, a ketolide antibiotic that is a substrate for both cyp3a and p-glycoprotein. ## Methods: Healthy volunteers given 3 different oral dose levels of abt-773 were genotyped at 2 common cyp3a5 and 7 common mdr-1 polymorphisms. individuals were categorized as cyp3a5-positive if they carried at least 1 functional cyp3a5\*1 allele and as cyp3a5-negative if they did not. area under the plasma concentration-time curves (aucs) from 0 to 6 hours (auc(t)) and maximum postdose plasma concentration (c(max)) after a single dose and on day 5 of a twice-daily regimen were calculated and correlated with genotypes. ## Results: Abt-773 auc(t) and c(max) were, on average, higher in cyp3a5-negative

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Author

KATZ, D

Publisher

Nature Publishing Group; Wiley (Blackwell Publishing); Wiley-Blackwell; Wiley; Springer Science and Business Media LLC; Research Square (ISSN 0009-9236)

Published

2004

Language

EN

Field

Medicine (Health Sciences)