title: The pharmacokinetics, pharmacodynamics, and tolerability of liraglutide, a once-daily human GLP-1 analogue, after multiple subcutaneous administration in healthy Chinese male subjects.
abstract: In this single-center, randomized, double-blind, within dose group, placebo-controlled, dose escalation trial, the pharmacokinetics, pharmacodynamics, tolerability, and safety of liraglutide were evaluated in 37 healthy Chinese subjects. Subjects were randomized to 1 of 3 dose groups (0.6, 1.2, or 1.8 mg), and within each group, randomized to liraglutide or placebo (3:1). All subjects started at 0.6 mg liraglutide (or placebo) once daily for 1 week, and the dose was increased for dose groups 1.2 mg and 1.8 mg in weekly steps of 0.6 mg to the predefined dose targets. Liraglutide or placebo was administered once daily by subcutaneous injection for 21 consecutive days. The dose relationships of AUC(0-24h), C(max), and C(trough) at steady state do not deviate in a relevant way from dose proportionality. t(max) and t(1/2) were 8 hours (median) and 11.2 to 12.2 hours (geometric mean), respectively. The plasma glucose levels in all liraglutide groups were decreased, while reduced serum insulin level was observed in the 1.2- and 1.8-mg groups after liraglutide treatment. The most common adverse events were of gastrointestinal origin. Other adverse events were comparable between the liraglutide and placebo groups. Liraglutide was well tolerated in healthy Chinese subjects. No major safety concerns were identified.
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Jiang
authors.forename: Jianyan
authors.initials: J
authors.lastname: Zhang
authors.forename: Lisbeth V
authors.initials: LV
authors.lastname: Jacobsen
authors.forename: Pei
authors.initials: P
authors.lastname: Hu
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D001786:Blood Glucose / Q000032:analysis; D003967:Diarrhea / Q000139:chemically induced; D004311:Double-Blind Method; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1