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

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Kattel K, Evande R, Tan C, Mondal G, Grem JL, Mahato RI

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

Br J Clin Pharmacol. 2015 Aug;80(2):267-75. doi: 10.1111/bcp.12620. Epub 2015 Jun 11.

PubMed ID

25752914 [ View in PubMed

]

Abstract

AIM: This study evaluated the influence of CYP2C19 polymorphisms on the pharmacokinetics of nelfinavir and its metabolite M8 in patients with pancreatic cancer. METHODS: 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. RESULTS: 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) microg ml(-1) , while that of CYP2C19*1/*2 patients was 3.60 (n = 1) and 6.14 +/- 0.31 (n = 5) microg 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) microg ml(-1) , while those of CYP2C19*1/*2 patients were 1.01 (n = 1) and 1.23 +/- 0.15 (n = 5) microg 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 microg ml(-1) .h and for CYP2C19*1/*2 patients, AUC(0,12 h) was 28.20 (n = 1) and 40.22 +/- 3.17 (n = 5) microg ml(-1) .h at the doses of 625 and 1250 mg nelfinavir twice daily, respectively. The Cmax of nelfinavir was significantly higher (P <0.05) in CYP2C19*1/*2 patients but there was no statistical difference in AUC(0,12 h). CONCLUSION: CYP2C19*1/*2 genotype modestly affected the pharmacokinetic profiles of nelfinavir and M8 in patients with locally advanced pancreatic cancer.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Nelfinavir	Cytochrome P450 2C19	Protein	Humans	No	Substrate Inducer	Details