Pharmacologic Advantages of Negative-Balance Isolated Pelvic Perfusion: Achievement of Intensive Exposure of the Pelvis to Platinum without Systemic Leakage

Abstract

To study tissue platinum concentrations and the correlation between tissue and plasma platinum concentrations after negative-balance isolated pelvic perfusion (NIPP) in a porcine model. All animal experiments were conducted according to the University Guidelines for Animal Care and Experimentation. Cisplatin (5 mg per kilogram of body weight) was administered into balloon catheter-isolated porcine pelvic circulations (n=7) and also systemically to a control group (n=7). Platinum concentrations in pelvic blood, systemic blood, urine, pelvic tissues (uterus, bladder, lymph nodes, and muscles), and kidneys were measured. Maximum platinum concentration (maximum serum drug concentration [C-max]) and area under the blood concentration-time curve (AUC) were compared between the two groups. With NIPP, pelvic C-max (58.4 mg/L) and AUC (1163.6 mg⋅min/L) were 44.9- and 56.2-fold higher than systemic C-max (1.3 mg/L) and AUC (20.7 mg⋅min/L), respectively, whereas the corresponding values in the control group were almost identical. Tissue platinum concentrations in pelvic organs were 2.8-5.6-fold higher than the control values. Platinum concentrations in kidney tissue were markedly lower with NIPP (1.0 mg/L) compared with the controls (8.1 mg/L). High platinum concentrations in pelvic tissues correlated well (P<.01) with high pelvic C-max and AUC. The pharmacologic advantages of NIPP were evident, with achievement of high platinum C-max, AUC, and high pelvic tissue concentrations without exposing systemic organs to platinum.