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Constant intraperitoneal 5‐fluorouracil infusion through a totally implanted system
Author(s) -
Gyves John W,
Ensminger William D,
Stetson Philip,
Niederhuber John E,
Meyer Mark,
Walker Suzette,
Janis Mary Ann,
Gilbertson Susan
Publication year - 1984
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1984.12
Subject(s) - bolus (digestion) , medicine , pharmacokinetics , peritoneal cavity , fluorouracil , peritoneum , urology , catheter , toxicity , anesthesia , surgery , chemotherapy , pharmacology
Five‐day continuous intraperitoneal (ip) infusions of 5‐fluorouracil (FU) were injected into five patients as part of a phase 1 clinical pharmacology study. They received 20 courses through a totally implanted catheter/injection port system. Six courses are evaluable for kinetic parameters and all courses are evaluable for toxicity. In each course a 2 to 3 log FU concentration differential in favor of the peritoneal cavity was achieved and maintained. Steady‐state venous plasma FU concentrations averaged 0.34 µM, whereas steady‐state ip FU concentrations averaged 697 µM. Mean total body clearance (TBC) in these patients was 18.4 l/min and mean permeability‐area (PA) product for diffusion from the peritoneum was 13.7 ml/min. Mean TBC of 20 l/min with ip FU infusion was observed in one patient who also received a 24‐hr IV FU infusion for comparison. The TBC during the later infusion was 5.9 l/min. In this patient, calculations indicate 75% extraction of drug during the passage from the peritoneum to the systemic circulation, presumably representing in large part hepatic extraction of FU taken into the portal venous circulation. Ip constant infusion and bolus kinetics were compared in one patient. TBC for the ip bolus was 14.3 l/min, which was approximately half of the TBC of 29.5 l/min determined during the 5‐day constant ip infusion. Thus constant ip infusion of FU (1 gm/day) can provide an improved regional advantage over bolus ip FU because of an increased TBC. Toxicity was acceptable in all courses. Dose limiting toxicity was regional, namely moderate chemical peritonitis seen in two of the five patients on repeated courses. There was no myelosuppression, alopecia, nausea, or vomiting. There were no infectious complications. The only patient with measurable disease had an objective response in hepatic metastases from gastric cancer. The implanted device was well tolerated and facilitated peritoneal fluid sampling. Clinical Pharmacology and Therapeutics (1984) 35, 83–89; doi: 10.1038/clpt.1984.12