Studies on the absorption of practically water-insoluble drugs following injection VIII: comparison of the subcutaneous absorption rates from aqueous suspensions in the mouse, rat, and rabbit.

Subcutaneous drug absorption rates from aqueous suspensions were measured in the mouse and the rabbit by a local clearance method and compared with those in the rat. A plot of the cube root of the residual fraction (W/W0) of the drug at the injection site versus time (t) gave a good linear relationship for the former two species. This implied that the kinetic equation for the absorption process in the rat, (W/W0)1/3 = 1 - jt, could be applied to them. In addition, the absorption rate constants (j) of the mouse and rabbit were close to that of the rat when the drug concentration (C0) in the suspension and the injection volume (V0) were fixed. These results led to the presumption that the correlation between j and C0 or V0 in the mouse and rabbit might be similar to that in the rat, and therefore, drug plasma levels for the former two at any dose might be roughly predictable even from one j value of the rat. The validity of this assumption was confirmed by comparison of the observed and predicted plasma concentrations after different subcutaneous doses of aqueous suspensions of N1-acetylsulfamethoxazole in the mouse and rabbit. These findings strongly supported the idea that for the subcutaneous administration of the drug in aqueous suspension under fixed dose per body weight, the rate of bioavailability should decrease with animal size, and therefore, the plasma drug level in larger species is not likely to be as high as that expected, from the data obtained for smaller species.