Pharmacokinetics of alogliptin when administered with food, metformin, or cimetidine: a two-phase, crossover study in healthy subjects
| Autor: | P Covington, X Li, M Davenport, R Christopher, Aziz Karim, E Wann, Q Mekki, P Fleck |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Administration Oral Dipeptidyl peptidase-4 inhibitor Type 2 diabetes Pharmacology Food-Drug Interactions Young Adult Pharmacokinetics Piperidines medicine Humans Hypoglycemic Agents Pharmacology (medical) Drug Interactions Cimetidine Uracil Dipeptidyl-Peptidase IV Inhibitors Cross-Over Studies business.industry Middle Aged medicine.disease Crossover study Metformin Tolerability Histamine H2 Antagonists Area Under Curve Female business Alogliptin medicine.drug |
| Zdroj: | International journal of clinical pharmacology and therapeutics. 48(1) |
| ISSN: | 0946-1965 |
| Popis: | Objective The dipeptidyl peptidase-4 inhibitor alogliptin, under development for treatment of Type 2 diabetes, primarily is excreted renally. This study investigated (1) the effect of food on alogliptin pharmacokinetics and tolerability and (2) pharmacokinetic interactions between alogliptin and metformin or cimetidine and tolerability of alogliptin when administered with either drug. Methods This randomized, open-label, two-phase, crossover study recruited healthy adults. In the single-dose phase, 36 subjects received an oral dose of alogliptin 100 mg under fed or fasted conditions. In the multiple-dose phase, subjects in one arm (n = 17) received 6 days each of alogliptin 100 mg once daily (q.d.), metformin 1,000 mg twice daily (b.i.d), and alogliptin q.d. + metformin b.i.d; subjects in the other arm (n = 18) received 6 days each of alogliptin 100 mg q.d., cimetidine 400 mg q.d., and alogliptin q.d. + cimetidine b.i.d. Pharmacokinetic parameters were determined after the last dose in each period. Tolerability was assessed through adverse events and clinical findings. Results Food had no effect on alogliptin area under the concentration-time curve (AUC) from 0 h to infinity and a small, clinically insignificant effect on maximum plasma concentration (C(max)) (fed/fasted least squares (LS) geometric mean ratio, 0.856; 90% confidence interval (CI), 0.798 - 0.917). Metformin and cimetidine did not affect alogliptin pharmacokinetics. Alogliptin had no effect on metformin C(max) and a small, clinically insignificant effect on AUC over the dosing interval ((alogliptin + metformin)/metformin LS geometric mean ratio, 1.19; 90% CI, 1.095 - 1.291). Alogliptin did not affect cimetidine pharmacokinetics. Alogliptin tolerability was similar under all conditions. Conclusion Alogliptin can be administered without regard to meals and with metformin or cimetidine without the need for dose adjustment. |
| Databáze: | OpenAIRE |
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