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Pharmacodynamics
New pharmacodynamics data have been reported by researchers at Boehringer Ingelheim GmbH
November 7th, 2009
According to recent research published in the journal Current Medical Research and Opinion, "Linagliptin (BI 1356) is a novel, orally available inhibitor of dipeptidyl peptidase-4 (DPP-4). Linagliptin improves glycaemic control in type 2 diabetic patients by increasing the half-life of the incretin hormone glucagon-like peptide-1 (GLP-1)." "Linagliptin is expected to be used as monotherapy or in combination with other antihyperglycaemic agents. This study was conducted to investigate potential pharmacokinetic or pharmacodynamic interactions between linagliptin and metformin. This randomised, monocentric, open-label, two-way crossover design study was conducted in 16 healthy male subjects. Linagliptin ( 10 mg/day) and metformin ( 850 mg three times daily) were each administered alone and concomitantly. The steady-state pharmacokinetics of linagliptin and metformin and the inhibition of DPP-4 activity were determined at the end of each dosing period. Co-administration of linagliptin had no apparent effect on metformin exposure (metformin AUC(tau, SS); geometric mean ratio [GMR] co-administration: individual administration was 1.01; 90% confidence interval [CI] was 0.89-1.14). Effects on maximum concentration (C-max, (ss)) were small (GMR: 0.89; 90% CI: 0.78-1.00). Co-administration of metformin did not significantly affect C-max,C- ss of linagliptin (GMR: 1.03; 90% CI: 0.86-1.24), but increased AUC(tau,ss) by 20% (GMR: 1.20; 90% CI: 1.07-1.34). Metformin alone had no effect on DPP-4 activity, and the inhibition of DPP-4 caused by linagliptin was not affected by concomitant administration of metformin. Tolerability was good whether linagliptin and metformin were administered alone or concomitantly. No serious adverse events occurred and the frequency of adverse events was low; 7 events in 6 subjects. The most frequent events were related to the gastrointestinal tract, as expected with metformin. Importantly, no subjects experienced signs or symptoms relating to episodes of hypoglycaemia. In this small, multiple dose study carried out in healthy subjects, co-administration of linagliptin with metformin did not have a clinically relevant effect on the pharmacokinetics or pharmacodynamics of either agent," wrote E.U. Graefemody and colleagues, Boehringer Ingelheim GmbH. The researchers concluded: "This study suggests linagliptin and metformin can safely be administered concomitantly in type 2 diabetes patients without dose adjustment; larger, longer-term clinical trials in diabetic patients are underway." Graefemody and colleagues published their study in Current Medical Research and Opinion (Evaluation of the potential for steady-state pharmacokinetic and pharmacodynamic interactions between the DPP-4 inhibitor linagliptin and metformin in healthy subjects. Current Medical Research and Opinion, 2009;25(8):1963-1972). For additional information, contact E.U. Graefemody, Boehringer Ingelheim Pharma GmbH & Co. KG, Drug Metab & Pharmacokinet, Birkendorfer Str 65, D-88397 Biberach, Germany. The publisher's contact information for the journal Current Medical Research and Opinion is: Librapharm, Informa Healthcare, Telephone House, 69-77 Paul Street, London EC2A 4 Lq, England. Keywords: Germany, Biberach, Diabetes, Dipeptidyl Peptidase, Drug Development, Drugs, Endocrinology, Enzyme Research, Enzymes, Enzymology, Glucagon Hydrochloride, Glycemic Control, Hormones, Hypoglycemic Agent, Metformin, Peptidase, Pharmaceuticals, Pharmacodynamics, Pharmacokinetics, Proteins, Proteomics, Therapies, Therapy, Treatment, Boehringer Ingelheim GmbH. This article was prepared by NewsRx editors from staff and other reports. Copyright 2009, NewsRx.com.
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