A pharmacokinetic (PK) study and a bioequivalence (BE) study were conducted to investigate the PK characteristics and safety of lubiprostone in healthy Chinese subjects and to evaluate the BE between the test and the reference drugs. The PK study consisted of a fasting state cohort (a single dose of 24 µg of lubiprostone), a 2-period crossover fasting and fed state cohort (a single dose of 48 µg of lubiprostone), and a multiple-dose cohort (24 µg of lubiprostone twice daily). The BE study was a single-dose, 2-treatment, 4-period, replicated crossover study. The plasma concentration of 15-OH-lubiprostone (M3) was measured by high-performance liquid chromatography-tandem mass spectrometry. The PK parameters were calculated using the noncompartment model with Phoenix WinNonlin. After a single dose of 24 ug of lubiprostone, the main PK parameters of M3 were 49.2 pg/mL, 74.0 h/pg/mL, and 1.1 hours for maximum plasma concentration (Cmax ), area under the plasma concentration time curve from time 0 to the last time point, and t1/2 , respectively. The main PK parameters of M3 showed dose-proportional characteristics in the dose range of 24-48 µg. Food affects the PK parameters of M3. Compared to the fasting state, time to maximum plasma concentration was delayed, Cmax decreased slightly, while AUC increased significantly under the fed state. The test and reference products had similar PK parameters and were bioequivalent in the fed state.
Keywords: bioequivalence; food effect; lubiprostone; multidose; pharmacokinetic; single-dose.
© 2023, The American College of Clinical Pharmacology.