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Population pharmacokinetics of pregabalin in healthy subjects and patients with chronic pain or partial seizures
Author(s) -
Bockbrader Howard N.,
Burger Paula,
Knapp Lloyd,
Corrigan Brian W.
Publication year - 2011
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2010.02933.x
Subject(s) - pregabalin , medicine , pharmacokinetics , population , volume of distribution , renal function , anesthesia , chronic pain , pharmacology , physical therapy , environmental health
Summary Purpose: Pregabalin, a high‐affinity ligand for α2δ subunits of voltage‐gated calcium channels, is a novel pharmacotherapy for chronic pain, partial seizures, and other disorders. The present study investigated the population pharmacokinetics of pregabalin following single and multiple doses in healthy volunteers and patient populations. Methods: Using nonlinear mixed‐effect modeling, 5,583 plasma pregabalin concentration–time samples from 1,723 subjects were analyzed: 2,868 samples from healthy volunteers or subjects with renal impairment (n = 123), 1,513 from patients with partial seizures (n = 626), and 1,202 from patients with chronic pain (n = 974). A one‐compartment model with first‐order elimination and absorption processes and absorption lag time was used. Key Findings: This pharmacostatistical model showed that: (1) pregabalin oral clearance (CL/F) was directly proportional to creatinine clearance (CLcr), but was independent of gender, race, age, female hormonal status, daily dose, and dosing regimen; (2) apparent volume of distribution was dependent on body weight and gender; (3) absorption rate was decreased when given with food; and (4) coadministration with marketed antiepileptic drugs (AEDs) had no significant effect on pregabalin CL/F. Significance: Pregabalin CL/F is related to CLcr, and this relationship is similar among healthy volunteers and patients with either partial seizures or chronic pain disorders. The only factor having a clinically significant influence on steady‐state plasma pregabalin concentrations is renal function.