Kinetics of peritoneal drug transport in rats: an application of the pore theory of transcapillary exchange.
In order to quantitatively describe the peritoneal transport of drugs, this paper proposes a kinetic model that is based on the hydrodynamic pore theory of transcapillary exchange, and incorporates an explicit description of volume and osmolality changes in the dialysate. Sulfisoxazole (SIX) and benzoic acid (BA) were used as model compounds. Following intraperitoneal administration of dialysate in rats, the osmolality, volume, and drug concentration in the dialysate were measured with respect to time. The obtained data were analyzed to give hydrodynamic parameters for solvent and a solute (including drug) by a computer-aided curve-fitting procedure according to the differential equations derived from the model. The present method, requiring no approximation of the changes in dialysate volume, made it possible to predict the concentration profiles of BA under different initial conditions of dialysate (i.e., different osmolality and volume). Solvent drag effect contributed little to the peritoneal transport of SIX and slightly to that of BA. It was also found that the peritoneal transport of BA is blood-flow limited while that of SIX is diffusion limited.
Nakashima
E
E
Hospital Pharmacy, Kanazawa University, Japan.
Ishikawa
F
F
Sato
H
H
Deguchi
Y
Y
Tamai
I
I
Matsushita
R
R
Ichimura
F
F
Tsuji
A
A
D000818:Animals; D001693:Biological Transport, Active; D001798:Blood Proteins / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009994:Osmolar Concentration; D010530:Peritoneal Dialysis; D004364:Pharmaceutical Preparations / Q000097:blood / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains
D001798:Blood Proteins; D004364:Pharmaceutical Preparations