Pharmacokinetics of levamisole in cancer patients treated with 5-fluorouracil.
OBJECTIVE
To investigate the pharmacokinetics of levamisole and a metabolite, p-hydroxylevamisole in patients with colorectal cancer treated with 5-fluorouracil (5-FU).


METHODS
Following an intravenous bolus dose of 5-FU, 20 patients with colorectal cancer received oral doses of 50 mg levamisole every 8 h for 3 days. Immediately after the last dose, blood and urine samples were collected over at least an 8-h period. Samples were assayed for levamisole and p-hydroxylevamisole by GC/MS. The levamisole plasma and urine data were subjected to pharmacokinetic analysis using NONMEM software.


RESULTS
Substantial interpatient variability was observed in the levamisole plasma concentration-time curves. Patients with cardiovascular or gastrointestinal complications demonstrated altered absorption of levamisole. Pharmacokinetic parameter values for levamisole were similar to those obtained previously in healthy subjects and other cancer patients.


CONCLUSIONS
There is no evidence that the pharmacokinetics of levamisole are altered by 5-FU administered immediately prior to levamisole administration. The relationship between the substantial intersubject variability in levamisole plasma concentration-time curves and clinical outcome following 5-FU/levamisole adjuvant chemotherapy should be examined.
Gwilt
P
P
UNMC/Eppley Cancer Center Core Pharmacokinetics Laboratory, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198-6025, USA.
Tempero
M
M
Kremer
A
A
Connolly
M
M
Ding
C
C
D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007978:Levamisole / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000964:Antimetabolites, Antineoplastic; D007978:Levamisole; D005472:Fluorouracil