Lack of effect of cisplatin on i.v. L-PAM plasma pharmacokinetics in ovarian cancer patients.

Melphalan (L-PAM) pharmacokinetics were investigated in nine ovarian cancer patients before and after cisplatin (DDP) treatment. When L-PAM was given 24 h before DDP, the elimination half-life (t 1/2 beta), plasma clearance (Clp), and volume of distribution (Vd beta) of L-PAM were, respectively: 46.4 +/- 6.7 min, 20.5 +/- 3.7 l/m2, and 306.8 +/- 34.4 ml/min per square meter. When L-PAM was inoculated 24 h after DDP, t 1/2 beta, Clp, and Vd beta were 47.5 +/- 6.3 min, 20.4 +/- 2.8 l/m2, and 322.0 +/- 54.1 ml/min per square meter. Thus, DDP pretreatment does not significantly affect L-PAM pharmacokinetics. Regression analysis showed a significant correlation between the L-PAM elimination rate constant (beta) and renal function assessed by creatinine clearance. One patient who received this sequence of treatment for six courses showed a threefold decrease of L-PAM Clp after the last treatment. The reported high myelotoxicity of the combination of DDP and L-PAM when DDP was given 24 h before L-PAM cannot be attributed to DDP-induced changes in L-PAM kinetics but might to some extent be related to a loss of renal function consequent to many courses of treatment.