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document
Pharmacokinetic- pharmacodynamic analysis of the role of CYP2C19 genotypes in short-term rabeprazole-based triple therapy against Helicobacter pylori . AIMS The aim was to explore the role of CYP2C19 polymorphism in short-term rabeprazole-based triple therapy against Helicobacter pylori infection . METHODS Patients with H. pylori infection were tested for CYP2C19 genotype as poor metabolizers ( PMs ) or extensive metabolizers ( EMs , homozygous EM or heterozygous EM ) and given rabeprazole for 7 days . Antibiotics ( clarithromycin and amoxicillin ) were given on days 1-4 , days 4-7 , or days 1-7 . A direct link model with an effect compartment was used in the population pharmacokinetic-pharmacodynamic analysis . The status of H. pylori infection was evaluated . RESULTS Rabeprazole clearance was lower in CYP2C19 PMs than in EMs ( with average values of 10.7 vs. 16.8 l h ( -1 ) in PMs and EMs , respectively ) , resulting in higher plasma levels in the former group . The values of EC ( 50 ) and k ( eo ) of gastrin response increased with multiple doses of rabeprazole . The k ( eo ) values were lower in CYP2C19 PMs than in EMs on day 1 ( 0.012 vs. 0.017 x 10 ( -4 ) l min ( -1 ) ) , and higher than in EMs on day 4 ( 0.804 vs. 0.169 x 10 ( -4 ) l min ( -1 ) ) of rabeprazole treatment . The predicted gastrin-time profile showed a higher response in CYP2C19 PMs than in EMs on days 4 and 7 . Helicobacter pylori was eradicated in all CYP2C19 PMs except in one patient infected by a resistant strain . In contrast , in CYP2C19 EMs the eradication rates ranged from 58 to 85 % . CONCLUSIONS CYP2C19 genotypes play a role in H. pylori eradication therapy . Rabeprazole-based short-term triple therapy may be applicable in CYP2C19 PMs for H. pylori eradication .
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Intervention_Pharmacological
rabeprazole-based triple therapy
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Intervention_Pharmacological
rabeprazole-based triple therapy
40841
Intervention_Pharmacological
rabeprazole
40842
Intervention_Pharmacological
Antibiotics
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Intervention_Pharmacological
clarithromycin and amoxicillin
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Intervention_Pharmacological
Rabeprazole
40845
Intervention_Pharmacological
rabeprazole
40846
Intervention_Pharmacological
rabeprazole
40847
Intervention_Pharmacological
Rabeprazole-based short-term triple therapy
40848
Outcome_Physical
H. pylori infection
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Outcome_Physical
Rabeprazole clearance
40850
Outcome_Physical
values of EC ( 50 )
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Outcome_Other
and
40852
Outcome_Physical
k ( eo ) of gastrin response
40853
Outcome_Physical
k ( eo ) values
40854
Outcome_Other
predicted gastrin-time profile
40855
Outcome_Other
Helicobacter pylori
40856
Outcome_Other
eradicated
40857
Outcome_Other
eradication rates