Exenatide pharmacokinetics in healthy Chinese subjects

Objectives: Exenatide is an adjunctive treatment for Type 2 diabetes. This was the first study to evaluate the pharmacokinetics, safety and tolerability of therapeutic doses (5 mu g and 10 mu g) of exenatide after single and multiple subcutaneous injections in healthy adult Chinese subjects. Methods: 24 healthy volunteers were randomized to receive either 5 mu g or 10 mu g of exenatide by subcutaneous injection. Subjects received a single injection of exenatide on Day 1, twice daily on Days 2 and 3, and once on Day 4. Serial blood samples were drawn for pharmacokinetic assessment at pre-dose and up to 12 h post dose on Day 1 and Day 4. Adverse events, vital signs. 12-lead ECG, body weight and clinical laboratory evaluations were assessed. Results: Exenatide, 5 mu g and 10 mu g, was rapidly absorbed with a median t(max) of 1 h after single and multiple doses. Exenatide C-max and AUC(t,ss) were (geometric mean (90% CI)) 145 (119 - 176) pg/ml and 370 (297 - 460) pg x h/ml, respectively, after multiple dosing with 5 mu g. The C-max and AUC(t,ss) were 311 (271 - 357) pg/ml and 878 (785 - 983) pg x h/ml, respectively, for 10 mu g. Mean half-life (t(1/2), range 0.99 - 1.25 h), apparent volume of distribution (V-7/F, 19.2 - 22.31), and apparent clearance (CL/F, range 11.4 - 13.5 l/h) remained consistent between single and multiple doses and across the two dose levels. Both the accumulation ratios and linearity index approached 1.0. The most common adverse events increased with dose, such that 8% of subjects who received 5 mu g and 42% of subjects who received 10 mu g experienced adverse events. Conclusions: Exenatide was rapidly absorbed, with similiar pharmacokinetic properties following single and multiple doses. Exenatide exposure after multiple doses approximately doubled from 5 mu g to 10 mu g.