Blood concentration of pantoprazole sodium is significantly high in hepatogenic peptic ulcer patients, especially those with a poor CYP2C19 metabolism

Abstract

OBJECTIVE: To determine the plasma concentration of pantoprazole sodium by high performance liquid chromatography and its distribution in patients with different CYP2C19 genotypes in an attempt to provide experimental data for the clinical dosage adjustment of the drug. METHODS: Patients with liver disease and associated peptic ulcer were genotyped according to their CYP2C19 wild‐type sequences and mutations in CYP2C19m1 and CYP2C19m2 by the principles of the American Surgical Association using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). The plasma concentration of pantoprazole sodium was detected after oral administration of the enteric‐coated capsules in all patients. Included in the present study were 21 patients with primary liver cancer complicated by pathogenic peptic ulcers (confirmed by endoscopy), 22 patients with fatty liver and 25 healthy volunteers between January 2006 and October 2007. The subjects were administered orally with pantoprazole sodium at 40 mg/day for 1 week consecutively. The drug concentration was detected at 24 h and 1 week after drug administration by drawing 3.0 mL blood from the cubital vein. RESULTS: The plasma concentration of pantoprazole sodium was related to the CYP2C19 enzyme type. The plasma concentration of extensive metabolizers (EM) was lower than that of poor metabolizers (PM) in the healthy control group at day 7 of drug administration. Regardless of PM or EM, the plasma concentration of pantoprazole sodium in primary liver cancer patients was higher than that in fatty liver patients, and even higher than that in healthy controls (P < 0.05). CONCLUSION: These results suggest that CYP2C19 activity is inversely correlated with the severity of liver disease, especially in PM patients.

Effects of CYP2C19, MDR1, and interleukin 1-B gene variants on the eradication rate of Helicobacter pylori infection by triple therapy with pantoprazole, amoxicillin, and metronidazole

“…This finding is in line with data reported by Sim et al [12], who estimated that CYP2C19*17 homozygotes would attain up to 40% lower omeprazole AUC values than subjects homozygous for the CYP2C19*1 allele after a single dose of the drug. Similar to our observations, higher pantoprazole concentrations in poor CYP2C19 metabolizers have been reported by others [11].…”

“…It was demonstrated that PPI-based eradication therapy is more effective, not only in PMs, but also in intermediate metabolizers (IM), heterozygotes with one wild-type and one defective CYP2C19 allele, compared with wild-type homozygotes (rapid extensive metabolizers) [8][9][10]. In PMs and IMs mean plasma levels of PPIs are higher, what makes therapy with standard drugs' doses more effective compared with wild-type homozygotes [11]. Recently, a novel CYP2C19 gene variant (CYP2C19*17), associated with increased gene transcription, and thus faster metabolism of CYP2C19 substrates was described [12].…”

Cytochrome P450 2C19 inhibitory activity of common berry constituents

“…Thus interactions of anthocyanins and CYP2C19 are not to be expected unless hepatic function is severely compromised or enzyme functionality is otherwise impaired, e.g. by inactivating genetic variation (Shao et al, 2009).…”

Influence of number of calibration standards within a defined range on pharmacokinetic disposition—case studies with omeprazole and clopidogrel carboxylic acid

“…It is not uncommon to construct calibration curves that cover a more than 100-fold range in order to characterize the pharmacokinetics from starting low human doses to the anticipated maximum tolerated dose (MTD) in fi rst-in-man clinical protocols and also for application in bioequivalence/pharmacokinetic studies (Vijaya Bharathi et al, 2009;Zhang and Chen, 2009;Tang et al, 2009;Zeng et al, 2009;Jiang et al, 2009;Arnold et al, 2008;Handy et al, 2008;Minkin et al, 2008;Jain et al, 2008;Xue et al, 2007;Zeng et al, 2007;Xu et al, 2007;Shen et al, 2004;Upreti et al, 2003). Additionally, the existence of a 100-fold range may be useful when dealing with NCEs that are substrates for polymorphic cytochrome P450 (CYP) isozymes wherein logorders of diff erences in the plasma concentrations of the parent and/or metabolite are expected to occur between the extensive metabolizer and poor metabolizer phenotypes (Preskorn et al, 2009;Shao et al, 2009;Davies et al, 2008;Stamer et al, 2007;Shilbayeh and Tutunji, 2006;Inomata et al, 2005).…”