Abstract
Purpose
Taspoglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist that
has >90% homology with the endogenous GLP-1 while retaining equivalent potency. Once-weekly
subcutaneous injections with taspoglutide demonstrated meaningful antihyperglycemic
and weight loss effects in patients with type 2 diabetes. The present study was performed
to compare the relative bioavailability of taspoglutide injected subcutaneously in
the abdomen, upper arm, and thigh.
Methods
Healthy overweight/obese subjects were randomized in an open-label, 3-way crossover
study. A single 20-mg dose of taspoglutide was injected subcutaneously on 3 occasions
in the abdomen, upper arm, or thigh. Each injection was separated by a 12-week washout
period. Blood was sampled up to 12 weeks for the pharmacokinetic evaluation of taspoglutide.
Findings
Sixty subjects were randomized into the study (mean age, 45.5 years; body weight,
97.6 kg; and body mass index, 31.4 kg/m2). AUClast values (geometric mean) for subcutaneous injections in the abdomen, upper arm, and
thigh were 44.2, 61.2, and 50.0 ng·h/mL, respectively. The geometric mean ratio (relative
bioavailability) for the upper arm versus the abdomen was 1.41 (90% CI: 1.22–1.62)
and for the thigh versus the abdomen was 1.13 (90% CI: 0.98–1.31). Corresponding Cmax values for subcutaneous injections in the abdomen, upper arm, and thigh were 0.268,
0.382, and 0.341 ng/mL, respectively, and the geometric mean ratio for the upper arm
versus the abdomen was 1.43 (90% CI: 1.24–1.64) and for the thigh versus the abdomen
was 1.27 (90% CI: 1.10–1.46). Decreases in taspoglutide exposure were observed with
each subsequent period. AUClast values (geometric mean across injections sites) for periods 1, 2, and 3 were 97.2,
42.6, and 31.5 ng·h/mL, respectively. The geometric mean ratio for period 2 versus
1 was 0.44 (90% CI: 0.38–0.50) and for period 3 versus 1 was 0.32 (90% CI: 0.27–0.37).
Analysis of pharmacokinetic data after first injection only (period 1) showed comparable
AUClast across the 3 injection sites and lower initial Cmax after injection into the abdomen compared with the other 2 injection sites. Overall,
taspoglutide was well tolerated by most subjects in all 3 injection sites, with a
lower incidence of nausea and vomiting when injected in the abdomen.
Implications
Regardless of a pronounced period effect, relative bioavailability of taspoglutide
was different across injection sites, with the lowest exposure and incidence of nausea
and vomiting seen after administration in the abdomen. In the absence of comparable
bioavailability, taspoglutide was recommended to be injected into the abdomen.
Key words
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Article info
Publication history
Published online: September 24, 2015
Accepted:
August 22,
2015
Identification
Copyright
© 2015 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.
