Influence of thiopurine S ‐methyltransferase polymorphisms in mercaptopurine pharmacokinetics in healthy volunteers

The objective of this study was to evaluate the role ofTPMT polymorphisms on the pharmacokinetics of mercaptopurine. For that purpose, we used collected pharmacokinetic data from 48 healthy volunteers (all males) who received a single oral dose of mercaptopurine 50 mg in two bioequivalence studies. The volunteers were subsequently genotyped forTPMT *2, *3A, *3B and *3C alleles by real ‐time PCR. There were four carriers (8.3%) ofTPMT*2 andTPMT*3A alleles. Mercaptopurine elimination was affected byTPMT loss ‐of‐function polymorphisms, since heterozygous subjects show 18% higher half‐life compared to wild‐type individuals. This fact is consistent with the expected since the presence of loss‐of‐function alleles decreasesTPMT enzymatic activity and, thus, affects mercaptopurine elimination. Moreover, mercaptopurine pharmacokinetic parameters were different among races, since Latins showed higher plasma concentrations and lower clearance compared to Caucasians. This fact might be due to a different distribution of polymorphisms in genes, other thanTPMT, that also influence the pharmacokinetics of mercaptopurine.

Source: Basic and Clinical Pharmacology and Toxicology - November 15, 2018 Category: Drugs & Pharmacology Authors: Miriam Saiz ‐Rodríguez, Dolores Ochoa, Carmen Belmonte, Manuel Román, Cristina Martínez‐Ingelmo, Lucía Ortega‐Ruíz, Carmen Sarmiento‐Iglesias, Coral Herrador, Francisco Abad‐Santos Tags: ORIGINAL ARTICLE Source Type: research