title: Pregabalin controlled-release pharmacokinetics in healthy volunteers: analysis of four multiple-dose randomized clinical pharmacology studies.
abstract: Pregabalin (Lyrica(®)) is approved as an immediate-release (IR) formulation for administration twice (BID) or three times (TID) a day depending on indication. Once daily (QD) dosing may be appropriate for ease of clinical use and patient convenience.
  
  
  
  The objectives of this analysis were: (1) to evaluate the pharmacokinetics of pregabalin controlled-release (CR) administered with food relative to the pregabalin IR formulation administered fasted; (2) to evaluate the pharmacokinetics of a two-tablet dose of pregabalin CR compared with the equivalent one-tablet dose of pregabalin CR; and (3) to determine the safety and tolerability of multiple-dose administration of pregabalin CR and IR.
  
  
  
  The pharmacokinetic properties of pregabalin CR were determined in four phase I, open-label, multiple-dose crossover studies (18-24 participants/study). Pregabalin CR (82.5, 165, 330 or 660 mg/day) administered QD was compared with pregabalin IR (75, 150, 300 or 600 mg/day, respectively) administered either BID or TID. Blood samples were collected up to 24 h post-dose. Pharmacokinetic parameters were estimated from plasma concentration-time data using standard noncompartmental methods. Adverse events were monitored throughout all studies.
  
  
  
  Eight-four healthy participants (19-55 years of age) received pregabalin. For all pregabalin CR doses, total exposure was equivalent to the corresponding pregabalin IR dose. Relative bioavailability of pregabalin CR was 93-97 % of pregabalin IR, and bioequivalence criteria with respect to the 24-h steady-state exposure (area under the plasma concentration-time curve from 0 to 24 h [AUC24]) were met. Administration of a two-tablet dose of pregabalin CR was bioequivalent to one-tablet pregabalin CR. The relative bioavailability of two-tablet pregabalin CR was 97-102 % of one-tablet pregabalin CR, and bioequivalence criteria with respect to AUC24 and peak plasma concentrations were met. Pregabalin CR pharmacokinetic parameters were dose proportional following administration of 82.5-660 mg/day pregabalin CR. Pregabalin was well tolerated across studies, with no serious or severe adverse events.
  
  
  
  Total daily exposure with multiple-dose pregabalin CR is equivalent to the corresponding pregabalin IR dose.
authors: Pfizer Inc, Eastern Point Road, Groton, CT, 06340, USA, Marci.L.Chew@pfizer.com.
authors: Marci L
authors: ML
authors: Chew
authors: Christine W
authors: CW
authors: Alvey
authors: Anna
authors: A
authors: Plotka
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; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005502:Food; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069583:Pregabalin; D013607:Tablets; D013810:Therapeutic Equivalency; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D000700:Analgesics; D003692:Delayed-Action Preparations; D013607:Tablets; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid