Influence of osmotic pressure and viscosity on intestinal drug absorption. I. Studies on the gastric effluent following oral administration of various quinine solutions to rats.

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Abstract
Variations in osmotic pressure, viscosity, gastric emptying rate and drug concentration in the gastric effluent following oral administration of quinine solutions prepared with various amounts of sucrose or sodium carboxymethyl cellulose (CMC-Na) were examined. The osmotic pressure of the gastric effluent after the administration of a hypertonic or hypotonic quinine solution tended to approach isotonicity with increase of the elapsed time after administration. In the case of a high viscosity solution, there was a gradual decrease in the viscosity of the effluent, while in the case of a low viscosity solution, little difference was seen between the original viscosity and that of the effluent during the overall time course. The solution administered was diluted in the stomach and thereafter flowed out at a definite quinine concentration. This concentration was varied by the effects of the added agents, sucrose and CMC-Na. In the absence of these agents, the quinine concentration of the effluent was the highest among the test solutions and the concentration decreased markedly with increasing osmotic pressure. Osmostic pressure had a greater influence on the quinine concentration of the effluent than did viscosity. The time course of the cumulative volume of effluent differed with each test solution. The ratio of quinine amount remaining in the stomach per dose vs. time was expressed in terms of a biexponential expression for all the test solutions except for the most hypertodnic solution. The gastric emptying rate estimated from the curves mentioned above was greatly influenced by osmotic pressure rather than viscosity and decreased with increase in osmotic pressure.