Prophylactic use of anti-emetic medications reduced nausea and vomiting associated with exenatide treatment: a retrospective analysis of an open-label, parallel-group, single-dose study in healthy subjects.
OBJECTIVE
Transient nausea and, to a lesser extent, vomiting are common adverse effects of exenatide that can be mitigated by dose titration and usually do not result in treatment discontinuation. This retrospective analysis of data from a phase 1, open-label, parallel-group, single-dose study in healthy subjects evaluated the effect of oral anti-emetics on exenatide-associated nausea and vomiting and on the pharmacokinetics of exenatide.


METHODS
A single subcutaneous dose (10 μg) of exenatide was administered to 120 healthy subjects (19-65 years, BMI 23-35 kg/m(2) ). Incidences of nausea and vomiting were compared between 60 subjects premedicated with two oral anti-emetics 30 min before the exenatide dose and 60 non-premedicated subjects. Similarly, the area under the concentration-time curve (AUC) and the maximum observed concentration (C(max) ) of plasma exenatide concentrations over 8 h post-dose were compared.


RESULTS
Among all subjects [61% male, 32 ± 12 years, body mass index (BMI) 29.1 ± 3.4 kg/m(2) (mean ± sd)], mild to moderate nausea was the most frequent adverse event after exenatide dosing. Vomiting was also observed. Subjects premedicated with anti-emetics experienced significantly less nausea and vomiting (16.7 and 6.7%, respectively) vs. non-premedicated subjects (61.7 and 38.3%, respectively; P-value <0.0001 for both nausea and vomiting). The mean area under the concentration-time curve and the maximum observed concentration AUC and C(max) of plasma exenatide concentrations during 8 h post-dose were not significantly different between groups.


CONCLUSIONS
Administration of oral anti-emetics before a single 10-μg exenatide dose was associated with significant reductions in treatment-emergent nausea and vomiting, with no discernible effect on the pharmacokinetics of exenatide. Use of anti-emetic therapy may provide a short-term strategy to minimize the nausea and vomiting associated with exenatide treatment.
Ellero
C
C
Amylin Pharmaceuticals Inc., San Diego, CA 92121, USA. cellero@amylin.com
Han
J
J
Bhavsar
S
S
Cirincione
B B
BB
Deyoung
M B
MB
Gray
A L
AL
Yushmanova
I
I
Anderson
P W
PW
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D015992:Body Mass Index; D004305:Dose-Response Relationship, Drug; D000077270:Exenatide; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D010455:Peptides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014481:United States; D014688:Venoms / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy*; D055815:Young Adult
D000932:Antiemetics; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D000077270:Exenatide