Usefulness of Intraperitoneal Carboplatin Administration : Pharmacokinetic Analysis

A bolus of carboplatin (CBDCA) 200～450mg/body (148～292mg/m^2) with 500ml saline was administrated into the abdominal cavity (ip) of 4 patients with ovarian cancer and 2 patients with uterine endometrial cancer, and concentrations of free and total platinum (ip) in the blood and ascites were measured with the passage of time. Moreover, the results were analyzed with a 2-compartment model and moment analyses in order to study in vivo kinetics of CBDCA at the time of the ip administration. 1) The shift of Pt to blood through ip administration depended on the peritoneal clearance. Cmax in blood was seen one hour after ip in patients with a normal peritoneum, and was seen between 4 and 6 hours after ip in patients with peritonitis carcinomatosa. The level was lower in the latter group. 2) The non-binding rate of Pt with protein in the ascites at the time of the ip administration was correlated with the CBDCA concentration in the ascites. 3) The non-binding rate was 80% or more both in the ascites and in the blood within 4 hours after ip. The high level of the nonbinding rate appeared to cause prolongation of the presence of the free-Pt in the ascites and blood, especially in patients with peritonitis carcinomatosa. 4) AUC level in blood was equal to or higher than that observed when the same dose was administered iv. The levels of free-Pt and AUC in the abdominal cavity were 2 to 5 times higher than those ill blood in patients with a normal peritoneum, and 7 to 14 times higher in patients with peritonitis carcinomatosa. 5) As to clinical effects, reduction of pleural effusion was observed in a patient and complete remission of ascites was obtained in a patient. The main side effect was myelosuppression. CBDCA-ip resulted in AUC levels in blood comparable to or higher than those achieved with CBDCA-iv. Since this ip administration led to AUC levels in the abdominal cavity that were several times higher than those achieved with CDDP and le d to longer duration of the presence of free-Pt due to its lower protein non-binding rate, the usefulness of this administration, which is equally, or more effective than CDDP, was clarified.