This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kirkwood, J. M. Articles by Frei, E. Search for Related Content PubMed PubMed Citation Articles by Kirkwood, J. M. Articles by Frei, E., III

Comparison of Pharmacokinetics of 5-Fluorouracil and 5-Fluorouracil with Concurrent Thymidine Infusions in a Phase I Trial¹

Divisions of Medical Oncology and Clinical Pharmacology, Sidney Farber Cancer Institute, Boston, Massachusetts 02165

The serum half-life of 5-fluorouracil (5-FUra) in humans is best described as a biexponential decay function, with t_1/2 = 7.8 ± 2.6 (S.E.) min and t_1/2 ß = 36.8 ± 13.5 min during initial courses of this drug alone. Pharmacokinetics of 5-FUra during courses of daily therapy (for 5 days) revealed prolongation of t_1/2 in both components of the decay curve, which has not been previously reported. Despite the efficacy of thymidine (dThd) given as a continuous i.v. infusion of 8 g/sq m/day in prevention of high-dose methotrexate toxicity, continuous infusion of dThd at this dose does not prevent the toxicity of 5-FUra or reverse inhibition of DNA and RNA synthesis by 5-FUra. On the contrary, continuous infusion of dThd appears to increase the toxicity of 5-FUra in all respects. Pharmacokinetic studies of 5-FUra during continuous dThd infusion revealed prolongation of the 5-FUra t_1/2 which remained stable through the course of 5 days of 5-FUra with dThd. This protracted t_1/2 is believed to account at least in part for the increased toxicity of 5-FUra with dThd. Dose-limiting mucositis, myelosuppression, and gastrointestinal toxicity were observed at 5-FUra doses ranging from one-half to two-thirds the customarily tolerated dose of 5-FUra alone in similar courses of daily bolus therapy (for 5 days).

¹ Supported by Grant CA-19589 from the National Cancer Institute, NIH.

² To whom requests for reprints should be addressed, at Department of Medicine, Section of Medical Oncology, Yale University School of Medicine, New Haven, Conn. 06510.

³ Present address: Department of Internal Medicine, University of Michigan, Ann Arbor, Mich. 48103.

Received 4/30/79. Accepted 10/ 4/79.