Clinical pharmacokinetics of pregabalin in healthy volunteers.
Pregabalin has shown clinical efficacy for treatment of neuropathic pain syndromes, partial seizures, and anxiety disorders. Five studies in healthy volunteers are performed to investigate single- and multiple-dose pharmacokinetics of pregabalin. Pregabalin is rapidly absorbed following oral administration, with peak plasma concentrations occurring between 0.7 and 1.3 hours. Pregabalin oral bioavailability is approximately 90% and is independent of dose and frequency of administration. Food reduces the rate of pregabalin absorption, resulting in lower and delayed maximum plasma concentrations, yet the extent of drug absorption is unaffected, suggesting that pregabalin may be administered without regard to meals. Pregabalin elimination half-life is approximately 6 hours and steady state is achieved within 1 to 2 days of repeated administration. Corrected for oral bioavailability, pregabalin plasma clearance is essentially equivalent to renal clearance, indicating that pregabalin undergoes negligible nonrenal elimination. Pregabalin demonstrates desirable, predictable pharmacokinetic properties that suggest ease of use. Because pregabalin is eliminated renally, renal function affects its pharmacokinetics.
Pfizer Global Research & Development, 50 Pequot Ave, New London, CT 06320, USA. Howard.Bockbrader@pfizer.com
Howard N
HN
Bockbrader
Louis L
LL
Radulovic
Edward L
EL
Posvar
James C
JC
Strand
Christine W
CW
Alvey
Janice A
JA
Busch
Edward J
EJ
Randinitis
Brian W
BW
Corrigan
George M
GM
Haig
Rebecca A
RA
Boyd
David L
DL
Wesche
D000284:Administration, Oral; D000328:Adult; D000700:Analgesics / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine
D000700:Analgesics; D000927:Anticonvulsants; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid