Estimation of the area under the concentration-time curve of racemic lansoprazole by using limited plasma concentration of lansoprazole enantiomers.

objectiveThe purpose of this study was to identify the common time point that gives plasma concentrations of lansoprazole enantiomers that adequately reflect the AUC of racemic lansoprazole.

methodsA randomized, double-blind, placebo-controlled, crossover study in three phases was conducted at intervals of 2 weeks. Eighteen healthy Japanese volunteers, including three CYP2C19 genotype groups, took a single 60-mg oral dose of lansoprazole after 6 days of pretreatment, with either clarithromycin (800 mg/day), fluvoxamine (50 mg/day), or a placebo. Multiple linear regression analysis was used to identify the most informative sampling times of (R)- and (S)-lansoprazole, using one to three samples to estimate the AUC(0-infinity) of racemic lansoprazole.

resultsThe best R(2) in each prediction formula for the AUC of racemic lansoprazole using one, two, and three sampling points of (R)- and (S)-lansoprazole based on the data sets from all three pretreatment groups (n = 54) were 0.897, 0.930, and 0.929, respectively. The best prediction formula for the AUC of racemic lansoprazole, using the fewest sampling points of (R)- and (S)-lansoprazole, was AUC = 6.5 x C(3h) of (R)-lansoprazole + 13.7 x C(3h) of (S)-lansoprazole - 9,917.3 x G1 - 14,387.2 x G2 + 7,103.6 (P < 0.001), where C(3h) is the plasma concentration 3 h after administration, G1 = 1 for the homozygous extensive metabolizer (EM) and 0 for the other genotypes, G2 = 1 for the heterozygous EM and 0 for the other genotypes.

conclusionsC(3h) monitoring of (R)- and (S)-lansoprazole is a useful time point to estimate the AUC of racemic lansoprazole. This method of plasma concentration monitoring at a few time points within 3 h might be more suitable for AUC estimation than CYP2C19 genotyping, particularly when lansoprazole is co-administered with CYP inhibitors.