Genetic epidemiology of induced CYP3A4 activity

TY - JOUR

T1 - Genetic epidemiology of induced CYP3A4 activity

AU - Rahmioglu, Nilufer

AU - Heaton, James

AU - Clement, Gail

AU - Gill, Raj

AU - Surdulescu, Gabriela

AU - Zlobecka, Karolina

AU - Hodgkiss, Dylan

AU - Ma, Yongmin

AU - Hider, Robert C.

AU - Smith, Norman W.

AU - Ahmadi, Kourosh R.

PY - 2011/10

Y1 - 2011/10

N2 - Aim The cytochrome P450 3A4 (CYP3A4) enzyme is implicated in the metabolism of more than 50% of all prescribed medications and its activity - including induced or inhibited activity - is deemed to be a crucial determinant of interindividual variability in drug disposition, poor therapeutic efficacy, and adverse response to medication. Methods We used the classical twin model in conjunction with an induction experiment to uncover the relative contribution of genetic and environmental factors to interindividual variation in induced CYP3A4 activity. A total of 367 healthy twins participated in the study. Each volunteer was administered a potent inducer of CYP3A4 (St John's Wort) for 14 days and the activity of CYP3A4 was quantified through the metabolism of the exogenously administered probe drug quinine sulfate. Results Baseline and induced CYP3A4 activity were highly variable with a seven-fold and 11-fold difference among our population, respectively. Alcohol consumption, BMI, and smoking were significantly associated with induced CYP3A4 activity, collectively explaining 20% of the variation (P

AB - Aim The cytochrome P450 3A4 (CYP3A4) enzyme is implicated in the metabolism of more than 50% of all prescribed medications and its activity - including induced or inhibited activity - is deemed to be a crucial determinant of interindividual variability in drug disposition, poor therapeutic efficacy, and adverse response to medication. Methods We used the classical twin model in conjunction with an induction experiment to uncover the relative contribution of genetic and environmental factors to interindividual variation in induced CYP3A4 activity. A total of 367 healthy twins participated in the study. Each volunteer was administered a potent inducer of CYP3A4 (St John's Wort) for 14 days and the activity of CYP3A4 was quantified through the metabolism of the exogenously administered probe drug quinine sulfate. Results Baseline and induced CYP3A4 activity were highly variable with a seven-fold and 11-fold difference among our population, respectively. Alcohol consumption, BMI, and smoking were significantly associated with induced CYP3A4 activity, collectively explaining 20% of the variation (P

U2 - 10.1097/FPC.0b013e3283498ecf

DO - 10.1097/FPC.0b013e3283498ecf

M3 - Article

VL - 21

SP - 642

EP - 651

JO - PHARMACOGENETICS AND GENOMICS

JF - PHARMACOGENETICS AND GENOMICS

IS - 10

ER -