Potential therapeutic levels of glucagon-like peptide I achieved in humans by a buccal tablet.
OBJECTIVE
Glucagon-like peptide I(7-36) (GLP-I) amide, an endogenous incretin, has been identified as a potential adjunct to the treatment of NIDDM and has been studied following intravenous and subcutaneous injection. A mucoadhesive buccal GLP-I tablet containing 119 nmol has been developed to provide transmucosal absorption as a possible alternative to injection treatment.


METHODS
Eight healthy volunteers received a single tablet under fasting conditions in this randomized double-blind placebo-controlled study. A total GLP-I immunoreactivity was measured using COOH-terminal radioimmunoassay (RIA) (total peptide activity) and NH2-terminal RIA (active, nondegraded peptide).


RESULTS
The mean (+/- SE) peak GLP-I concentration was 117 +/- 19 pmol/l and occurred 30 +/- 4 min after application. The mean placebo-adjusted area under curve was 8,145 +/- 873 pmol.min-1.l-1, consistent with a relative bioavailability of 7% versus intravenous injection and 47% versus subcutaneous injection. The levels of active peptide increased in parallel with total GLP-I. Half-life of peptide activity after buccal administration was 27 and 24 min measured with COOH-terminal and NH2-terminal RIA, respectively. Placebo adjusted insulin concentrations increased to a peak of 252 +/- 57 pmol/l, glucose decreased 1.4 +/- 0.2 mmo/l, and glucagon decreased 17 +/- 3 ng/l, consistent with the increase in plasma GLP-I concentrations.


CONCLUSIONS
Therapeutic plasma levels of GLP-I in humans were achieved after a single buccal tablet. No increased degradation of GLP-I was found in the buccal mucosa compared to subcutaneous tissue. This alternative treatment form may be feasible in in the future for NIDDM.
Gutniak
M K
MK
Vällingby Medical Center, Stockholm, Sweden. mark.gutniak@mailbox.swipnet.se
Larsson
H
H
Heiber
S J
SJ
Juneskans
O T
OT
Holst
J J
JJ
Ahrén
B
B
D000042:Absorption; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006207:Half-Life; D006801:Humans; D007328:Insulin / Q000097:blood; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D011863:Radioimmunoassay; D013607:Tablets
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D013607:Tablets; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon