Individual Difference in the Pharmacokinetics of a Drug, Pravastatin, in Healthy Subjects

Abstract

The purpose of this investigation was to determine whether there were individual pharmacokinetic differences of a drug, pravastatin. Furthermore, the percentage of subjects who showed pharmacokinetic differences was determined. A single oral dose of pravastatin 10 mg was administered to 84 Japanese healthy male subjects. Serum concentrations of pravastatin were measured for 8 hours postdose. Area under the concentration-time curve (AUC) and peak concentration (Cmax) were determined as primary evaluation parameters. An outlier was defined as follows: Outlier 1 < Q1 - (Q3 - Q1) x 1.5 or Q3+(Q3-Q1) x 1.5 < Outlier 1, Outlier 2 < Q1 - (Q3 - Q1) x 3 or Q3+ (Q3-Q1) x 3 < Outlier 2. Subjects who were outliers were regarded as having an individual difference in pharmacokinetic behavior. In AUC and Cmax, 4 of 84 subjects (4.8%) were higher outliers. Of these 4 subjects, 2 were high outliers in both AUC and Cmax. No subjects were low outliers. It was concluded that a significant individual difference in the pharmacokinetics of pravastatin was observed in 4.8% of the subjects (4/84).