Correlation analysis of CYP2B6 gene polymorphisms and pharmacokinetic parameters of isotretinoin in healthy human volunteers / 中华皮肤科杂志

ABSTRACT

Objective To evaluate the association between isotretinoin pharmacokinetic parameters and CYP2B6 (cytochrome p-450) gene polymorphisms. Methods Blood samples were collected at different time points from 21 healthy male volunteers who received a single 40-rng oral dose of isotretinoin. High performance liquid chromatography-electrospray ionization mass spectrometry (LC-MS) was used for the quantification of isotretinoin in plasma samples which were standardized by dosage and body weight. PCR and restriction fragment length polymorphism (RFLP) analysis were performed to detect the G516T mutation in exon 4 as well as A785G mutation in exon 5 of CYP2B6 gene in these subjects. Results There was an obvious genetic linkage imbalance in exon 4 and 5 of CYP2B6 gene among these volunteers. In the case of CYP2B6*4 allele,3 (14.29%) people were CYP2B6*4/*4 homozygotes, 6 (28.57%) CYP2B6*1/*4 heterozygotes, and 12 (57.14%) CYP2B6*1/*1 wild-type homogygotes, while as far as CYP2B6*6 allele was concerned, 3 (14.29%)people were CYP2B6*6/*6 homozygotes, 5 (23.81%) CYP2B6*1/*6 heterozygotes, and 13 (61.90%)CYP2B6*1/*1 wild-type homozygotes. The reaction half-time (t1/2) and mean residence time (MRT) of isotretinoin were longer in volunteers carrying wild-type CYP2B6*4 allele than those of CYP2B6*4/*4 homozygotes (both P ＜ 0.05 ), while no significant difference was observed in maximum concentration (Cmax), peak time (Tmax) or area under the plasma concentration time (AUC) between the two groups of volunteers. There was no statistical difference in any of the above parameters between subjects carrying wild type CYP2B6*6 allele and those of CYP2B6 *6/*6 homozygotes (all P ＞ 0.05 ). Conclusions The mutation of CYP2B6*4 allele ia relevant to the metabolism of isotretinoin, which seems to be more rapid in CYP2B6*4/*4 homozygotes.