Abstract

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 µg and 10 µg) of exenatide after single and multiple subcutaneous injections in healthy adult Chinese subjects. Methods: 24 healthy volunteers were randomized to receive either 5 µg or 10 µg 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 µg and 10 µg, 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 × h/ml, respectively, after multiple dosing with 5 µg. The C_max and AUC_t,ss were 311 (271 – 357) pg/ml and 878 (785 – 983) pg × h/ml, respectively, for 10 µg. Mean half-life (t_1/2, range 0.99 – 1.25 h), apparent volume of distribution (V_z/F, 19.2 – 22.3 l), 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 were gastrointestinal in nature and mild in severity. The frequency of adverse events increased with dose, such that 8% of subjects who received 5 µg and 42% of subjects who received 10 µg experienced adverse events. Conclusions: Exenatide was rapidly absorbed, with similar pharmacokinetic properties following single and multiple doses. Exenatide exposure after multiple doses approximately doubled from 5 µg to 10 µg.

Author Details

Authors

• X. Zhao¹
• Y.M. Cui¹
• Y. Zhou¹
• H.L. Zhang¹
• K.P. Yeo²
• H. Linnebjerg⁴
• L.S. Tham²
• P. Kothare³
• L.L. Teng²
• K. Mace³
• D. Soon²

Departments

• ¹ Peking University First Hospital, Beijing, People’s Republic of China,
• ² Lilly-NUS Center for Clinical Pharmacology, Singapore,
• ³ Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA, and
• ⁴ Eli Lilly and Company, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, UK

Address

Y.M. Cui, PhD; Department of Pharmacy, Peking University First Hospital, No. 6, Da Hong Luo Chang Street, Beijing, 100034, People’s Republic of China
Email: [email protected]

Citation