In vitro and in situ absorption of etamsylate. Part 2: In vitro and in situ properties.
The oil to water partition behaviour, the diffusion across artificial lipid barriers and the in situ gastro-intestinal absorption of the haemostatic etamsylate were studied. Very small partition coefficients were obtained (0.015-0.13) which are independent on the pH (range 1 to 6) and the nature of the organic phase (n-hexane, n-octanol, ethylacetate). Using the Sartorius membrane stimulator small diffusion constants were calculated both at phase I pH 6.0 (kd = 7.82.10(-3)cm.min-1) and especially at phase I pH 1.2 (kd = 4.7.10(-6) cm x min-1). The in situ absorption experiments on male Wistar rats showed very poor gastric absorption, but considerable intestinal absorption rate (absorption rate constant ka = 0.39 +/- 0.19 h-1, absorption half life t1/2(ka) = 1.94 +/- 0.60 h). The ion-pair diffusion across the intestinal wall seems to be the main reason responsible for the fast intestinal absorption. The obtained results are consistent to the literature data concerning etamsylate pharmacokinetics in vivo.
Yamboliev
I
I
Institute of Pharmacology and Pharmacy, Sofia, Bulgaria.
Nikova
T
T
Bogdanova
S V
SV
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004058:Diffusion; D004979:Ethamsylate / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D006490:Hemostatics / Q000378:metabolism*; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D006490:Hemostatics; D004979:Ethamsylate