Pregabalin controlled-release pharmacokinetics in healthy volunteers: analysis of four multiple-dose randomized clinical pharmacology studies

Clin Drug Investig. 2014 Sep;34(9):627-37. doi: 10.1007/s40261-014-0221-2.


Background: 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.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: Total daily exposure with multiple-dose pregabalin CR is equivalent to the corresponding pregabalin IR dose.

Trial registration: NCT01202435 NCT01220219 NCT01202422 NCT01257516.

Publication types

  • Clinical Trial, Phase I
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analgesics / administration & dosage
  • Analgesics / adverse effects
  • Analgesics / pharmacokinetics*
  • Area Under Curve
  • Biological Availability
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Food*
  • Humans
  • Male
  • Middle Aged
  • Pregabalin
  • Tablets
  • Therapeutic Equivalency
  • Young Adult
  • gamma-Aminobutyric Acid / administration & dosage
  • gamma-Aminobutyric Acid / adverse effects
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / pharmacokinetics


  • Analgesics
  • Delayed-Action Preparations
  • Tablets
  • Pregabalin
  • gamma-Aminobutyric Acid

Associated data