Pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) to patients with peritoneal carcinomatosis

The pharmacokinetics of cisplatin administered by continuous hyperthermic p eritoneal perfusion (CHPP) was characterized in patients with peritoneal ca rcinomatosis. Cisplatin was added into the perfusate with escalating doses from 100 mg/m(2) to 400 mg/m(2). The hyperthermic perfusion was maintained for 90 minutes with a flow rate of 1.5 L/min and a target peritoneal temper ature of 42.5 degrees C after a tumor debulking procedure. Samples of both the perfusate and blood were obtained during the perfusion and 30 minutes a fter the perfusion. Cisplatin plasma and perfusate concentrations were dete rmined by flameless atomic absorption spectrometry with a lower limit of de tection of 2 ng/ml and a coefficient of variation (CV) < 10%. Fifty-six pat ients were enrolled in the study. The mean (+/- SD) percentage of cisplatin present in the perfusate at the completion of perfusion was 27.8% +/- 20% of the total dose. The maximum cisplatin concentrations in the perfusate we re 10 times higher than those in plasma. The area under the concentration-t ime curve (AUC) of the perfusate was 13 times higher than the AUC of plasma . A two-compartment model with an additional peritoneal cavity compartment fits to the data best based on the Akaike information criterion. However, t he interpatient variability was considerably high (CV < 100%). In conclusio n, cisplatin administered by hyperthermic peritoneal perfusion resulted in a pharmacological advantage by obtaining higher and direct drug exposure to the tumor in the peritoneal cavity while limiting systemic absorption and toxicity. Using a complex two-compartment model, the authors were able to c haracterize the pharmacokinetics of cisplatin given intraperitoneally via t his technique. (C) 1999 the American College of Clinical Pharmacology.