Population pharmacokinetics and proton pump inhibitory effects of intravenous lansoprazole in healthy Japanese males.
A total of 56 healthy Japanese males were enrolled in single- or multiple- dose pharmacokinetic trials of intravenous lansoprazole administration. The population pharmacokinetics of the drug was evaluated using nonlinear mixed effects model (NONMEM) software. In addition, the effect of CYP2C19 polymorphism on proton pump inhibition by lansoprazole was investigated using 24-h intragastric pH monitoring in the 32 subjects. Time course of serum lansoprazole concentration following intravenous short infusion was well described by a 2-compartment model. The mean volume of the central and peripheral compartments was 0.110 and 0.201 l/kg, respectively. The mean inter-compartment clearance was estimated to be 0.0882 l/h/kg. The population mean value of systemic clearance in the homoEM (CYP2C19 1/ 1), heteroEM (CYP2C19 1/2 and 1/3), and PM (CYP2C19 2/2, 2/3, and 3/3) groups was 0.179, 0.109, and 0.038 l/h/kg, respectively. The mean intragastric pH following twice-daily doses of 30 mg lansoprazole was approximately 6, 5, and 4 in the PM, heteroEM, and homoEM groups, respectively. These findings indicate that large interindividual variability exists in the pharmacokinetics of intravenously administered lansoprazole, but that twice-daily infusion of a 30 mg dose leads to significant and sustained proton pump inhibition, even in the homoEM group, despite the short elimination half-life of the drug.
Graduate School of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Yuichi
Y
Sakurai
Masashi
M
Hirayama
Muneaki
M
Hashimoto
Takanori
T
Tanaka
Setsuo
S
Hasegawa
Shin
S
Irie
Kiyoshi
K
Ashida
Yuichiro
Y
Kayano
Masato
M
Taguchi
Yukiya
Y
Hashimoto
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000328:Adult; D000465:Algorithms; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D007564:Japan; D064747:Lansoprazole; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics; D017711:Nonlinear Dynamics; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology; D011153:Population; D054328:Proton Pump Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology*; D012016:Reference Values
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19