Clinical Pharmacology of Albiglutide, a GLP-1 Receptor Agonist

医学 兴奋剂 药理学 内分泌学 受体 安慰剂 杜拉鲁肽 利拉鲁肽 内科学 糖尿病 2型糖尿病 病理 替代医学
作者
Malcolm A. Young,Jeffrey Wald,Jessica Matthews,Rhona Scott,Rebecca J. Hodge,Hui Zhi,Rickey R. Reinhardt
出处
期刊:Postgraduate Medicine [Informa]
卷期号:126 (7): 84-97 被引量:31
标识
DOI:10.3810/pgm.2014.11.2836
摘要

AbstractAlbiglutide is a glucagon-like peptide-1 analogue composed of tandem copies of modified human glucagon-like peptide-1 (7–36) coupled to recombinant human albumin that is approved in adults for the treatment of type 2 diabetes mellitus. After subcutaneous administration, albiglutide is likely primarily absorbed via the lymphatic circulation, with maximum concentrations being reached in 3 to 5 days; steady-state exposures are achieved following approximately 4 to 5 weeks of once-weekly administration. The elimination half-life of albiglutide is approximately 5 days. Clearance of albiglutide is 67 mL/h with between-subject variability of 34.9%; no covariates have been identified that would require dose adjustment of albiglutide. Albiglutide lowers the fasting plasma glucose and reduces postprandial glucose excursions. In addition, β-cell secretion is enhanced by albiglutide during hyperglycemia, whereas secretion is suppressed during hypoglycemia; α-cell response to hypoglycemia is not impaired by albiglutide. Albiglutide does not prolong the corrected QT interval but has a modest effect on heart rate in patients with type 2 diabetes mellitus. Dose adjustment is not suggested in patients with renal impairment, but experience in patients with severe renal impairment is very limited, and it is recommended that albiglutide be used with care in such patients due to an increased frequency of diarrhea, nausea, and vomiting. No clinically relevant drug interactions have been observed in clinical trials. Trial Registration: NCT00938158, NCT01406262, NCT00537719, NCT01077505, NCT01147731, NCT01147718, NCT01147692, NCT00354536, NCT00394030, NCT00530309, NCT01357889, NCT00518115, NCT01098461, NCT01475734, NCT00849017, NCT00838916, NCT00839527, NCT01098539.Keywords: albiglutidetype 2 diabetes mellitusGLP-1pharmacokineticspharmacodynamicsglucose
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