Pharmacokinetics of alkylating metabolites of cyclophosphamide in different strains of mice

Determination of the amount of alkylating (NBP) metabolites of cyclophosphamide (CP) in blood serum of BALB/c and DBA/2 mice has revealed that the shape of the curve describing the accumulation of NBP-metabolites, depends on the administered drug dose and animals' genotype. The experimental data obtained made it possible to suggest an improved pharmacokinetic model which takes into account a possible switching in of factors conditioning non-linear changes in the intensity of the accumulation processes in blood and elimination of CP alkylating metabolites from blood. The effect of different CP alkylating metabolite kinetics in BALB/c and DBA/2 mice on a different sensitivity of these mice to the immunodepressive action of CP in vivo, has been discussed.