title: Effect of the gastrointestinal prokinetic agent erythromycin on the pharmacokinetics of pregabalin controlled-release in healthy individuals: a phase I, randomized crossover trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Pfizer Inc, Eastern Point Road, Groton, CT, USA, Marci.L.Chew@pfizer.com.
authors: Marci L
authors: ML
authors: Chew
authors: Anna
authors: A
authors: Plotka
authors: Christine W
authors: CW
authors: Alvey
authors: Verne W
authors: VW
authors: Pitman
authors: Tanja
authors: T
authors: Alebic-Kolbah
authors: Joseph M
authors: JM
authors: Scavone
authors: Howard N
authors: HN
authors: Bockbrader
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004917:Erythromycin / Q000494:pharmacology*; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069583:Pregabalin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D005765:Gastrointestinal Agents; D000069583:Pregabalin; D004917:Erythromycin