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

J. Glaholm, BSc, MRCP, FRCR M. O. Leach, PhD, MInstP ^* D. Collins, BA ^* B. Al Jehazi, FRCS J. C. Sharp, MSc ^* T. A. D. Smith, PhD ^* J. Adach, PhD ^* A. Hind, MSc V. R. McCready, DSc, MRCP, FRCR and H. White, FRCS

Academic Unit of Radiotherapy and Oncology, The Royal Marsden Hospital and The Institute of Cancer Research, Downs Road, Sutton, Surrey SM2 5PT ^* Nuclear Magnetic Resonance Unit and Joint Department of Physics, The Royal Marsden Hospital and The Institute of Cancer Research, Downs Road, Sutton, Surrey SM2 5PT Department of Surgery, The Royal Marsden Hospital and The Institute of Cancer Research, Downs Road, Sutton, Surrey SM2 5PT Department of Nuclear Medicine, The Royal Marsden Hospital and The Institute of Cancer Research, Downs Road, Sutton, Surrey SM2 5PT Siemens Ltd, Sunbury on Thames, Windmill Road, Middlesex TW16 7HS

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.

Received for publication February 1, 1989. Revision received November 1, 1989.