Pharmacokinetics of gabapentin in a novel gastric-retentive extended-release formulation: comparison with an immediate-release formulation and effect of dose escalation and food.
The objectives of the 3 phase I studies described herein were (1) to compare the pharmacokinetics of gabapentin delivered from a novel gastric-retentive dosage form vs an immediate-release formulation, (2) to assess the dose proportionality of the gastric-retentive extended-release formulation, and (3) to determine the effect of food on the pharmacokinetics of gabapentin delivered from this formulation. The time to reach maximum plasma concentration (t(max)) was extended for gabapentin delivered from the gastric-retentive extended-release formulation compared with the immediate-release formulation. A dose-related increase in both the maximum plasma concentration (C(max)) and the area under the plasma concentration-time curve (AUC) was observed as the gabapentin dose increased from 600 to 2400 mg. Fed status and increased fat content delayed t(max) and enhanced C(max) and AUC in proportion to the fat content. The pharmacokinetics of gabapentin delivered from this extended-release formulation allows a reduced dosing frequency while maintaining bioavailability and possibly diminishing the occurrence of adverse events attributable to a slower increase to the peak concentration compared with the immediate-release dosage form.
Chen
Cuiping
C
Depomed, 1360 O'Brien Drive, Menlo Park, CA 94025, USA. cchen@depomed.com
Cowles
Verne E
VE
Hou
Eddie
E
D000328:Adult; D000588:Amines / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004041:Dietary Fats / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018565:Food-Drug Interactions; D000077206:Gabapentin; D005746:Gastric Emptying / Q000187:drug effects; D005753:Gastric Mucosa / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
D000588:Amines; D018712:Analgesics, Non-Narcotic; D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D003509:Cyclohexanecarboxylic Acids; D003692:Delayed-Action Preparations; D004041:Dietary Fats; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin