Exenatide pharmacokinetics in healthy Chinese subjects.
OBJECTIVE
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 microg and 10 microg) of exenatide after single and multiple subcutaneous injections in healthy adult Chinese subjects.


METHODS
24 healthy volunteers were randomized to receive either 5 microg or 10 microg 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 microg and 10 microg, was rapidly absorbed with a median tmax of 1 h after single and multiple doses. Exenatide Cmax and AUCtau,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 microg. The Cmax and AUCtau,ss were 311 (271 - 357) pg/ml and 878 (785 - 983) pg x h/ml, respectively, for 10 microg. Mean half-life (t1/2, range 0.99 - 1.25 h), apparent volume of distribution (Vz/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 microg and 42% of subjects who received 10 microg 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 microg to 10 microg.
Zhao
X
X
Peking University First Hospital, Beijing, People's Republic of China.
Cui
Y M
YM
Zhou
Y
Y
Zhang
H L
HL
Yeo
K P
KP
Linnebjerg
H
H
Tham
L S
LS
Kothare
P
P
Teng
L L
LL
Mace
K
K
Soon
D
D
D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D000077270:Exenatide; D005260:Female; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007279:Injections, Subcutaneous; D008297:Male; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014688:Venoms / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D000077270:Exenatide