Impact of CYP2C19 polymorphism on the pharmacokinetics of nelfinavir in patients with pancreatic cancer

British Journal of Clinical Pharmacology
Krishna KattelRam I Mahato

Abstract

This study evaluated the influence of CYP2C19 polymorphisms on the pharmacokinetics of nelfinavir and its metabolite M8 in patients with pancreatic cancer. Nelfinavir was administered orally to patients for over 10 days. The plasma concentrations of nelfinavir and M8 were measured by HPLC. The genotypes of CYP2C19*1, CYP2C19*2 and CYP2C19*3 were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Pharmacokinetic profiles of nelfinavir and M8 were characterized by wide interindividual variability. The mean Cmax of nelfinavir in CYP2C19*1/*1 patients was 3.89 ± 0.40 (n = 3) and 5.12 ± 0.41 (n = 30) µg ml(-1) , while that of CYP2C19*1/*2 patients was 3.60 (n = 1) and 6.14 ± 0.31 (n = 5) µg ml(-1) at the doses of 625 and 1250 mg nelfinavir twice daily, respectively. For the M8 metabolite, the mean Cmax of CYP2C19*1/*1 patients was 1.06 ± 0.06 (n = 3) and 1.58 ± 0.27 (n = 30) µg ml(-1) , while those of CYP2C19*1/*2 patients were 1.01 (n = 1) and 1.23 ± 0.15 (n = 5) µg ml(-1) at the doses of 625 and 1250 mg nelfinavir twice daily, respectively. The area under the plasma concentration-time curve (AUC(0,12 h)) values of nelfinavir for CYP2C19*1/*1 patients were 28.90 ± 1.27 and 38.90 ± 4.99 µg m...Continue Reading

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Citations

Feb 1, 2017·Endocrine-related Cancer·Kirk JensenVasyl Vasko
Apr 27, 2018·BMC Medical Genomics·Joowon LeeTaesung Park
Dec 15, 2020·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Srinivas Reddy PallerlaThirumalaisamy P Velavan
Nov 25, 2020·Cancers·Mahbuba R Subeha, Carlos M Telleria
Feb 25, 2020·Anti-cancer Agents in Medicinal Chemistry·Sombeer SharmaArun K Sharma

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