Pharmacogenomics of CYP3A: considerations for HIV treatment.
The understanding of the cytochrome P450 3A SNP in antiretroviral therapy is important, because it is highly inducible, extremely polymorphic and metabolizes many of the drugs that are key components of highly active antiretroviral therapy regimens. This enzyme is prolific and promiscuous towards drug and xenobiotic substrate selection and it is also unpredictable among individuals, having a 5- to 20-fold variability in its ability to contribute to drug clearance. The importance of human CYP3A pharmacogenetics is also gaining attention in other established areas of pharmacotherapy as it may contribute to the goal of predicting efficacy and/or toxicity, specifically with the discovery of null allele CYP3A4*20. This review summarizes the current understanding, implications of genetic variation in the CYP3A enzymes, the central role of CYP3A in linking human genetics, the pharmacokinetics and resulting pharmacodynamic responses to certain antiretroviral drugs, and their eventual place in applied clinical pharmacotherapy.
Lakhman
Sukhwinder S
SS
Department of Pharmaceutical Sciences, DYC School of Pharmacy, Buffalo, NY 14201 USA.
Ma
Qing
Q
Morse
Gene D
GD
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005787:Gene Frequency; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide
D019380:Anti-HIV Agents; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A