5-Fluorouracil pharmacokinetics in patients with metastatic colorectal carcinoma after high-dose leucovorin.
The effect of high-dose leucovorin on 5-fluorouracil (5-FU) pharmacokinetics was studied in 5 patients with metastatic colorectal carcinoma. Patients received leucovorin, 500 mg/m2, and 5-FU, 600 mg/m2, on 1 day and 5-FU alone 1 week later. Plasma concentrations of 5-FU and 5-FU anabolites were determined over 2 hr. Levels of 5-FU were highest initially and then fell rapidly. Plasma concentration-time curves suggested a two-compartment kinetic model. Anabolite levels exceeded 5-FU levels after 15 min. When leucovorin was administered, the time of distribution (t1/2 alpha for 5-FU increased from 8.9 +/- 2.4 to 12.8 +/- 2.5 min (p < 0.0005) and the volume of distribution (Vd) increased from 0.129 +/- 0.039 to 0.237 +/- 0.033 L/kg (p < 0.03). Elimination and plasma clearance of 5-FU were unchanged. Anabolite levels were initially lower (p < 0.05) with leucovorin, suggesting increased tissue extraction of 5-FU.
Department of Surgery, Long Island Jewish Medical Center, New Hyde Park, New York 11042.
T A
TA
Stein
G P
GP
Burns
B
B
Bailey
M L
ML
Citron
D000368:Aged; D015179:Colorectal Neoplasms / Q000097:blood / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005472:Fluorouracil / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007275:Injections, Intravenous; D002955:Leucovorin / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008297:Male; D008875:Middle Aged
D002955:Leucovorin; D005472:Fluorouracil