Bioavailability of high-dose oral leucovorin

J D Hines; M H Zakem; D J Adelstein; P Giroski; M R Blum; Y M Rustum

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Journal article

Bioavailability of high-dose oral leucovorin

J D Hines, M H Zakem, D J Adelstein, P Giroski, M R Blum and Y M Rustum

NCI monographs, Vol.5, pp.57-60

1987

PMID: 3501547

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Abstract

Fifteen adult subjects comprised the study group; 2 were colon cancer patients. Total leucovorin (citrovorum factor; CF) doses of 200, 400, 800, and 1600 mg were equally subdivided and administered at 0, 1, 2, and 3 hours. Three of the subjects were fasting and the other 12 were not. Quantitation of serum L-CF by Pediococcus cerevisiae and total reduced folates (TRF) by radio-assay were performed in 10 samples from each subject drawn over a 12-hour period after initiation of CF dosing. The mean serum levels of L-CF remained greater than 0.1 microM at 3 hours and the TRF 3.5 microM at 5 hours, respectively, after termination of CF dosing in all subjects treated at the 800- and 1600-mg dose schedule. At all CF dosage schedules employed, peak serum concentrations were reached within 4 and 6 hours after initiation of oral CF. Peak TRF concentrations at the 200-, 400-, 800-, and 1600-mg doses were 3.42 +/- 0.65, 4.05 +/- 1.04, 4.81 +/- 0.14, and 5.11 +/- 1.81 microM, respectively. Peak L-CF levels at 200, 400, 800, and 1600 were 0.15 +/- 0.11, 0.21 +/- 0.14, 0.23 +/- 0.11, and 0.34 +/- 0.16 microM. Based upon these observations, the following conclusions were reached: 1) no significant differences were observed in serum concentrations of folates between the 800- and 1600-mg dose schedules; 2) at these doses serum concentrations of L-CF and TRF were achieved that warrant a phase I investigation of high-dose oral CF with standard dose FUra in patients with advanced colorectal carcinoma.

Administration, Oral

Adult

Biological Availability

Colonic Neoplasms - drug therapy

Dose-Response Relationship, Drug

Female

Folic Acid - blood

Humans

Leucovorin - administration & dosage

Leucovorin - pharmacokinetics

Male

Middle Aged

Details

Title: Subtitle: Bioavailability of high-dose oral leucovorin
Creators: J D Hines - Division of Hematology/Oncology, Cleveland Metropolitan General Hospital, OH 44109
M H Zakem
D J Adelstein
P Giroski
M R Blum
Y M Rustum
Resource Type: Journal article
Publication Details: NCI monographs, Vol.5, pp.57-60
PMID: 3501547
ISSN: 0893-2751
Language: English
Date published: 1987
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984359863902771

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