Studies on the absorption of practically water-insoluble drugs following injection VII: plasma concentration after different subcutaneous doses of a drug in aqueous suspension in rats.
The response patterns of the time profile of plasma drug level to dose elevation after subcutaneous administration of a practically water-insoluble drug in aqueous suspension were investigated. Equations to predict the plasma drug concentration at any time and the time Tmax at which it reaches the maximum (Cmax) at different doses were derived using empirical equations describing the subcutaneous absorption kinetic process as an input function of one- and two-compartment models. Computer simulation for the one-compartment model showed that Cmax tended to increase curvilinearly with dose elevation accompanied by the retardation of Tmax. It also showed that this tendency was noticeable in dose elevation at fixed injection volume and became more significant for drugs with a smaller absorption rate and/or a larger elimination rate. This suggested that a more effective means of raising the drug plasma level for such drugs would be improvement of the formulation. The validity of the information obtained from the simulation was confirmed by various subcutaneous administration experiments of N1-acetylsulfamethoxazole aqueous suspensions in rats. Further, the multiple-point injection method was ascertained to be useful for avoiding the nonlinear increase in plasma drug concentration with dose elevation appearing in the subcutaneous administration of aqueous suspensions.
D000042:Absorption; D000818:Animals; D007279:Injections, Subcutaneous; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D013420:Sulfamethoxazole / Q000031:analogs & derivatives / Q000378:metabolism; D013535:Suspensions
D004364:Pharmaceutical Preparations; D013535:Suspensions; C021281:N(1)-acetylsulfamethoxazole; D013420:Sulfamethoxazole