Abstract
BackgroundHyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface-spreading malignancies to maximize local drug concentrations while minimizing systemic effects. The pharmacokinetic advantage of HIPEC is defined as the intraperitoneal to intravascular ratio of drug concentrations. We hypothesized that body surface area (BSA) would correlate with the pharmacokinetic advantage of HIPEC. Because oxaliplatin is administered in 5 % dextrose, we hypothesized that BSA would correlate with glycemia.MethodsWe collected blood and peritoneal perfusate samples from ten patients undergoing HIPEC with a BSA-based dose of 250 mg/m2 oxaliplatin, and measured drug concentrations by inductively coupled plasma mass spectrophotometry. We monitored blood glucose for 24 h postoperatively. Areas under concentration-time curves (AUC) were calculated by trapezoidal rule. Pharmacokinetic advantage was calculated by (AUC[peritoneal fluid]/AUC[plasma]). We used linear regression to test for statistical significance.ResultsHigher BSA was associated with lower plasma oxaliplatin AUC (p = 0.0075) and with a greater pharmacokinetic advantage (p = 0.0198) over the 60-minute duration of HIPEC. No statistically significant relationships were found between BSA and blood glucose AUC or peak blood glucose levels.ConclusionsHigher BSA is correlated with lower plasma drug levels and greater pharmacokinetic advantage in HIPEC, likely because of increased circulating blood volume with inadequate time for equilibration. Plasma glucose levels after oxaliplatin HIPEC were not clearly related to BSA.
Highlights
Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surfacespreading malignancies to maximize local drug concentrations while minimizing systemic effects
Higher body surface area (BSA) is correlated with lower plasma drug levels and greater pharmacokinetic advantage in HIPEC, likely because of increased circulating blood volume with inadequate time for equilibration
The use of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with oxaliplatin has been reported for peritoneal carcinomatosis from colorectal cancer, ovarian carcinoma, pseudomyxoma peritonei, and malignant peritoneal mesothelioma.[1]
Summary
Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surfacespreading malignancies to maximize local drug concentrations while minimizing systemic effects. The pharmacokinetic advantage of HIPEC is defined as the intraperitoneal to intravascular ratio of drug concentrations. We hypothesized that body surface area (BSA) would correlate with the pharmacokinetic advantage of HIPEC. Because oxaliplatin is administered in 5 % dextrose, we hypothesized that BSA would correlate with glycemia. We collected blood and peritoneal perfusate samples from 10 patients undergoing HIPEC with a BSAbased dose of 250 mg/m2 oxaliplatin, and measured drug concentrations by inductively coupled plasma mass spectrophotometry. Pharmacokinetic advantage was calculated by (AUC[peritoneal fluid]/ AUC[plasma]). Higher BSA was associated with lower plasma oxaliplatin AUC (p = 0.0075) and with a greater pharmacokinetic advantage (p = 0.0198) over the 60-minute duration of HIPEC. No statistically significant relationships were found between BSA and blood glucose AUC or peak blood glucose levels
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