Time‐Dependent Amplified Pharmacokinetic and Pharmacodynamic Responses of Rabeprazole in Cytochrome P450 2C19 Poor Metabolizers

Abstract

The pharmacokinetic and pharmacodynamic data suggest that CYP2C19 poor metabolizers might be subject to advantageous conditions, especially after day 4, for treating H. pylori infection with rabeprazole.

Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice

“…After 8 days of dosing, the mean pH values were 5.9, 4.7, and 4.1 (respectively) (Shirai et al, 2001), and the percentage of time with a pH Ͼ4 was significantly greater in PMs (ϳ92%) than in heterozygous EMs (72%) or homozygous EMs (37%) (compared with 3-6% with placebo) (Sagar et al, 2000). Most (Horai et al, 2001;Ieiri et al, 2001;Shirai et al, 2001;Lin et al, 2003) but not all (Adachi et al, 2000) of the studies with rabeprazole show the lowest intragastric pH in homozygous EMs. Thus, standard recommended doses of any of these PPIs might not provide sufficient acid suppression in homozygous EMs, suggesting that an increase in dose might be required in this group.…”

“…The AUCs of rabeprazole are also increased but less markedly in CYP2C19 deficiency (1.3-to 2.3-fold in heterozygous EMs and 3.0-to 5.3-fold in PMs) (Horai et al, 2001;Ieiri et al, 2001;Shirai et al, 2001;Lin et al, 2003). Individuals with CYP2C19 deficiency have superior acid suppression with conventional doses of omeprazole and lansoprazole (Furuta et al, 1999b;Sagar et al, 2000;Shirai et al, 2001) and presumably pantoprazole.…”

Role of Omeprazole Dosage and Cytochrome P450 2C19 Genotype in Patients Receiving Omeprazole‐Amoxicillin Dual Therapy for Helicobacter pylori Eradication

“…Genomic DNA was extracted from peripheral leukocytes of blood samples by using standard methods. 17 Genetic polymorphism of the CYP2C19*2 (CYP2C19 m1) and CYP2C19*3 (CYP2C19 m2) alleles was identified by PCR-RFLP as described previously. 18,19 Intragastric pH Measurements After an overnight fast at the end of day 7, the study patients came to the hospital and underwent 24-hour pH monitoring starting at 9:00 A.M. on day 8.…”

Actual Aspects of Anti-Secretor Therapy of Gastroesophageal Reflux Disease

“…Биодоступность других ИПП (омепразола, эзомепра-зола, лансопразола и пантопразола) зависит от генетиче-ского полиморфизма CYP 2C19 [29,30], что может быть причиной разных вариаций биодоступности и, как след-ствие, возможных неоднородных клинических результа-тов. Единственный ИПП, биодоступность которого не зависит от генетического полиморфизма CYP 2C19, -рабепразол, что обуславливает предсказуемость его кли-нического эффекта и хорошие результаты в эрадикации Helicobacter pylori [31], а также обеспечивает наимень-ший спектр лекарственных взаимодействий, что особен-но актуально у коморбидных пациентов при необходимо-сти приема других препаратов (клопидогрел, нестероид-ные противовоспалительные препараты, дигоксин, нифе-дипин, фенитоин, теофиллин и др.)…”