The effect of food with varying fat content on the clinical pharmacokinetics of gabapentin after oral administration of gabapentin enacarbil.
Gabapentin enacarbil, an actively transported prodrug of gabapentin, provides sustained and dose-proportional exposure to gabapentin.


OBJECTIVE
To evaluate the effect of food of varying fat content on the pharmacokinetics and tolerability of gabapentin enacarbil. METHODS, MATERIALS AND SUBJECTS: A randomized, open-label, crossover study of 1,200 mg gabapentin enacarbil was conducted in 12 healthy adults, under four conditions: fasted, or following low-fat (200 - 300 kcal total, approximately 6% from fat), moderate-fat (500 - 600 kcal total, approximately 30% from fat) or high-fat meals (1,000 kcal total, approximately 50% from fat), separated by a washout period of >or= 5 days.


RESULTS
Ten subjects completed treatment under all four conditions. Data from all subjects were used for pharmacokinetic and safety analyses unless stated otherwise. Mean (standard deviation) bioavailability (based on urinary recovery) of gabapentin from gabapentin enacarbil was 42.0 (6.1)% (fasted), 64.3 (13.2)% (low-fat meal), 64.9 (16.9)% (moderate-fat meal), and 76.1 (14.4)% (high-fat meal). Gabapentin exposures (AUC(inf)) in fed conditions were 23% (low-fat meal), 31% (moderate-fat meal), and 40% (high-fat meal) greater than the exposure under fasted condition. Fed conditions did not significantly delay median t(max), but a trend for delayed gabapentin enacarbil absorption was seen in t(max) ranges following moderate- and high-fat meals compared with the fasted state or low-fat meal. The most commonly reported treatment-emergent adverse events (TEAEs) were dizziness (4 subjects), balance disorder (4 subjects) and somnolence (3 subjects). All TEAEs were rated as mild in intensity.


CONCLUSIONS
Administration of gabapentin enacarbil with food enhanced gabapentin exposure compared with fasted conditions, regardless of the fat or caloric content, and gabapentin enacarbil was generally well tolerated.
XenoPort, Inc., Santa Clara, CA 95051, USA. ritu.lal@xenoport.com
R
R
Lal
J
J
Sukbuntherng
W
W
Luo
F J
FJ
Huff
J
J
Zou
K C
KC
Cundy
D000328:Adult; D000588:Amines / Q000493:pharmacokinetics; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002219:Carbamates / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003509:Cyclohexanecarboxylic Acids / Q000493:pharmacokinetics; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D018565:Food-Drug Interactions; D000077206:Gabapentin; D006801:Humans; D008297:Male; D008875:Middle Aged; D011355:Prodrugs; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
C493250:1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid; D000588:Amines; D000927:Anticonvulsants; D002219:Carbamates; D003509:Cyclohexanecarboxylic Acids; D004041:Dietary Fats; D011355:Prodrugs; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin