Comparison of 5-fluorouracil pharmacokinetics following intraperitoneal and intravenous administration using in vivo 19F magnetic resonance spectroscopy

Abstract

Intrahepatic pharmacokinetic studies of 5-Fluorouracil (5 FU) metabolism following intravenous and intraperitoneal administration have been undertaken in four patients using in vivo 19F nuclear magnetic resonance spectroscopy. Following intravenous administration, 5 FU decayed with "half times" ranging from 5 to 17 min. There was considerable variation of 5 FU pharmacokinetics between patients following intraperitoneal administration. Peritoneal contamination by infused 5 FU was considered to be a significant problem in one patient. A technique for providing superficial signal suppression was therefore investigated and its efficacy for excluding signal from the peritoneal space has been demonstrated. Owing to the potential for contamination from peritoneal 5 FU, the accumulation of fluoro-beta-alanine (FBAL) is a more reliable indicator of drug catabolism than the measurement of unlocalized "hepatic" 5 FU. Rapid intrahepatic catabolism of 5 FU to FBAL was demonstrated in all patients. However, there was greater pharmacokinetic variation following intraperitoneal administration than following intravenous administration. Therapeutic implications of intravenous compared with intraperitoneal administration of 5 FU are discussed.