Effect of the gastrointestinal prokinetic agent erythromycin on the pharmacokinetics of pregabalin controlled-release in healthy individuals: a phase I, randomized crossover trial
| Autor: | Howard N. Bockbrader, Marci L. Chew, Anna Plotka, Joseph M. Scavone, Christine Alvey, Verne Pitman, Tanja Alebic-Kolbah |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male medicine.medical_treatment Pregabalin Prokinetic agent Erythromycin Bioequivalence Young Adult Pharmacokinetics Gastrointestinal Agents medicine Humans Pharmacology (medical) Drug Interactions Adverse effect Cross-Over Studies business.industry General Medicine Middle Aged Crossover study Healthy Volunteers Tolerability Therapeutic Equivalency Anesthesia Area Under Curve Delayed-Action Preparations Anticonvulsants Female business medicine.drug |
| Zdroj: | Clinical drug investigation. 35(5) |
| ISSN: | 1179-1918 |
| Popis: | The controlled-release (CR) formulation of pregabalin is designed to remain in the stomach for a prolonged period while slowly releasing pregabalin for absorption in the small intestine. This study evaluated the effect of the gastrointestinal prokinetic agent, erythromycin, on the pharmacokinetics of a single dose of pregabalin CR 330 mg administered following an evening meal and the safety and tolerability of a single dose of pregabalin CR 330 mg when administered with and without multiple doses of erythromycin 500 mg. This was a phase I, open-label, randomized, two-period, two-treatment crossover study. Participants received (in a randomized sequence) a single oral dose of pregabalin CR 330 mg alone and pregabalin CR 330 mg co-administered with multiple doses of erythromycin 500 mg. The CR formulation was administered immediately following a standardized 600−750 calorie 30 % fat evening meal. Erythromycin 500 mg was administered orally approximately 1 h prior to pregabalin CR, as well as 6 and 12 h following the first erythromycin dose. Blood samples were collected up to 48 h post-pregabalin CR dose. Pharmacokinetic parameters were estimated from concentration–time data using standard noncompartmental methods. Adverse events were monitored throughout. Eighteen healthy participants (aged 19−52 years) received pregabalin CR. Co-administration of pregabalin CR with erythromycin resulted in a 17 % decrease in total exposure [area under the plasma concentration–time curve from zero to infinity (AUC∞)] and a 13 % decrease in peak plasma concentrations (C max) relative to pregabalin CR administered alone. The 90 % CI for the ratio of the adjusted geometric mean AUC∞ was 76.5−89.2 % (outside the 80−125 % range prespecified for bioequivalence). Adverse events were of mild to moderate severity and the adverse event profile was similar for pregabalin CR administered with and without erythromycin. Co-administration of multiple high doses of erythromycin resulted in 17 % lower pregabalin exposure for a single dose of pregabalin CR 330 mg than for pregabalin CR 330 mg administered alone. Although the two treatments did not achieve formal bioequivalence, the impact of co-administered erythromycin treatment was small and not considered clinically relevant. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|