To determine if dose dependency occurs with 2 weight-based single doses of omeprazole in a phenotyping study, as well as to quantitate 3-month intraindividual variability of CYP2C19 activity, 24 Caucasian subjects with body weights from 45 to 66 kg and 67 to 90 kg received single oral 30-mg and 40-mg doses of omeprazole, respectively. Female subjects were phenotyped during the mid-follicular and mid-luteal phases of their menstrual cycles for 3 complete cycles. Male subjects were phenotyped every 14 days for 12 weeks. Subjects with a body weight between 45 and 66 kg received an additional 40-mg omeprazole single dose on visit 7. The 2-hour postdose plasma concentration ratio of omeprazole to 5-hydroxyomeprazole was used as a measure of CYP2C19 activity. The percent coefficient of variation (CV%) of omeprazole phenotyping ranged from 6.3% to 51.3% (median = 18.5%, interquartile range = 14.8%-23.5%). Weight-based single doses of omeprazole for CYP2C19 phenotyping did not exhibit dose dependency. Therefore, a weight-based approach may improve the quantitation of omeprazole/metabolites.