OBJECTIVE: To clarify the pharmacological advantage of carboplatin-based intraperitoneal chemotherapy using the three-compartment mathematical model. METHODS: Eleven consecutive patients in one institution underwent intraperitoneal administration of carboplatin, and 11 consecutive patients in another institution received intravenous administration. Carboplatin (AUC=6 mg x min/ml) was diluted in 500 ml 5% glucose and administered either as an intraperitoneal bolus infusion or intravenous drip infusion during 1 h. Patients undergoing intravenous injection also received an infusion of 500 ml 5% glucose to obtain intraperitoneal samples. Intraperitoneal fluid and blood samples were obtained, immediately and 1, 2, 4, 8, 12, and 24 h after administration. The mathematical model consisting of a three-compartment model was applied to analyze the pharmacokinetics. The model was created with simultaneous differential equations and was solved by the Runge-Kutta method. RESULTS: The rate constants of platinum diffusion from the peritoneal cavity to serum, serum to peritoneal cavity, serum to peripheral space, peripheral space to serum, and elimination were 0.94+/-0.79 (mean+/-SD), 1.28+/-2.50, 16.50+/-9.26, 0.99+/-0.62, and 4.14+/-1.45 (h-1), respectively. When the theoretical pharmacological concentration of platinum was calculated using this mathematical model, 24-h platinum AUC in the serum was exactly the same regardless of intraperitoneal or intravenous administration of carboplatin. However, the 24-h platinum AUC in the peritoneal cavity was approximately 17 times higher when carboplatin was administered by the intraperitoneal route. CONCLUSION: The present pharmacological analysis suggests that intraperitoneal infusion of carboplatin is feasible not only as an intraperitoneal regional therapy but also as a more reasonable route for systemic chemotherapy.
OBJECTIVE: To clarify the pharmacological advantage of carboplatin-based intraperitoneal chemotherapy using the three-compartment mathematical model. METHODS: Eleven consecutive patients in one institution underwent intraperitoneal administration of carboplatin, and 11 consecutive patients in another institution received intravenous administration. Carboplatin (AUC=6 mg x min/ml) was diluted in 500 ml 5% glucose and administered either as an intraperitoneal bolus infusion or intravenous drip infusion during 1 h. Patients undergoing intravenous injection also received an infusion of 500 ml 5% glucose to obtain intraperitoneal samples. Intraperitoneal fluid and blood samples were obtained, immediately and 1, 2, 4, 8, 12, and 24 h after administration. The mathematical model consisting of a three-compartment model was applied to analyze the pharmacokinetics. The model was created with simultaneous differential equations and was solved by the Runge-Kutta method. RESULTS: The rate constants of platinum diffusion from the peritoneal cavity to serum, serum to peritoneal cavity, serum to peripheral space, peripheral space to serum, and elimination were 0.94+/-0.79 (mean+/-SD), 1.28+/-2.50, 16.50+/-9.26, 0.99+/-0.62, and 4.14+/-1.45 (h-1), respectively. When the theoretical pharmacological concentration of platinum was calculated using this mathematical model, 24-h platinum AUC in the serum was exactly the same regardless of intraperitoneal or intravenous administration of carboplatin. However, the 24-h platinum AUC in the peritoneal cavity was approximately 17 times higher when carboplatin was administered by the intraperitoneal route. CONCLUSION: The present pharmacological analysis suggests that intraperitoneal infusion of carboplatin is feasible not only as an intraperitoneal regional therapy but also as a more reasonable route for systemic chemotherapy.
Authors: Mark A Morgan; Michael W Sill; Keiichi Fujiwara; Benjamin Greer; Stephen C Rubin; Koen Degeest; S Diane Yamada; Steven Waggoner; Robert L Coleman; Joan L Walker; Robert S Mannel Journal: Gynecol Oncol Date: 2011-02-01 Impact factor: 5.482
Authors: Natalie Gould; Michael W Sill; Robert S Mannel; P H Thaker; Paul Disilvestro; Steve Waggoner; S Diane Yamada; Deborah K Armstrong; Lari Wenzel; Helen Huang; Paula M Fracasso; Joan L Walker Journal: Gynecol Oncol Date: 2011-12-11 Impact factor: 5.482
Authors: Bradley J Monk; Helen Q Huang; Robert A Burger; Robert S Mannel; Howard D Homesley; Jeffrey Fowler; Benjamin E Greer; Matthew Boente; Sharon X Liang; Lari Wenzel Journal: Gynecol Oncol Date: 2012-12-04 Impact factor: 5.482