Unbiased membrane permeability parameters for gabapentin using boundary layer approach.
The present study was performed to determine the relative contribution of both passive and nonpassive transport processes in jejunal absorption of gabapentin. The oral absorption of gabapentin was studied using in situ single pass intestinal perfusion technique in fasted rats. Unbiased intrinsic membrane absorption parameters such as maximal flux, Michaelis constant, carrier permeability, and membrane permeability were calculated using a modified boundary layer model. Gabapentin intestinal perfusion results indicate that its jejunal absorption in rats occurs via a nonpassive process, with no significant passive absorption component, as demonstrated by saturable absorption kinetics and its concentration-dependent permeability. A good correlation (r2 = 0.88) between observed human absorption fraction and calculated (from in situ rat intestine) human absorption fraction was obtained.
Madan
Jitender
J
Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Punjab 160 062, India.
Chawla
Garima
G
Arora
Vinod
V
Malik
Rajiv
R
Bansal
Arvind K
AK
D000465:Algorithms; D000588:Amines / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000493:pharmacokinetics*; D001692:Biological Transport; D002463:Cell Membrane Permeability; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry / Q000493:pharmacokinetics*; D004058:Diffusion; D000077206:Gabapentin; D006801:Humans; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism; D008297:Male; D010637:Phenolsulfonphthalein / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014867:Water; D005680:gamma-Aminobutyric Acid / Q000737:chemistry / Q000493:pharmacokinetics*
D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D014867:Water; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D010637:Phenolsulfonphthalein