Relationship between the blood concentration of the drug and its cumulative effect: a pharmacokinetic analysis of the nephrotoxic action of gentamicin and streptomycin.

The general principle of dependence of cumulative effects on drug concentration in the blood is proposed. The registered response is regarded as a result of the dual effect of drug blood level and duration of action. The corresponding experimental design consists in maintaining the serum concentration values at several definite levels and determining the response values for each of them. The constant serum level of the drug could be achieved by means of continuous infusion calculated according to the pharmacokinetic model. This principle was proved in the acute experiments on cats which established a relationship between the nephrotoxic effect of gentamicin and streptomycin on the one hand and their concentration in the serum and duration of action on the other.