5-Fluorouracil pharmacokinetics in patients with metastatic colorectal carcinoma after high-dose leucovorin.
1994
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 concentrationtime curves suggested a two-compartment kinetic model. Anabolite levels exceeded 5-FU levels after 15 min. When leucovorin was administered, the time of distribution (t1/2α 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.
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