Pharmacokinetics And Bioequivalence Studies Of Tegaserod In Healthy Volunteers

Objective: To estabilish an accurate and sensitive LC-MS method for determination oftegaserod in human serum; To determine the concentration of tegaserod in plasma after single and multiple oral doses tegaserod maleate tablet, and to investigate its pharmacokinetic characteristics in 10 Chinese healthy volunteers, including absorption, distribution, elimination and accumulation; To invaluate the bioequivalence of tegaserod maleate capsule, as test, and tegaserod maleate tablet, as reference, after single oral dose in 20 healthy Chinese volunteers in a randomized crossover test, and to provide datas for its application and clinical practice.Methods: Pharmacokinetics Single Dose Study 10 healthy Chinese volunteers, alluniversity students and half males half females, were enrolled in this study. A 12 mg of tegaserod maleate tablet were orally given and an aliquot of blood were collected before (Oh) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24h after administration. Blood samples were centrifuged at 3000rpm·min^-1 for 10 min and plasma was separated and stored at -20 ℃ for analysis.Multiple Doses Study After one week washout period, the same 10 healthy Chinese volunteers as in single dose study were orally given 12 mg of tegaserod maleate tablets once daily for seven days. An aliquot of blood were collected at 7:00 am of 5th, 6th and 7th day before and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24h of 7th day after 12 mg tegaserod maleate tablet. Blood samples were centrifuged at 3000rpm·min^-1 for 10 min and plasma was separated and stored at -20 ℃ for analysis.Determination of Tegaserod Plasma Concentration A Hypersil ODS₂(5μm, ID,4.0× 150mm) column and a mobile phase of 5mmol·L^-1 ammonium acetate-acetonitrile (27:73,...