Pharmacokinetics of levamisole in cancer patients treated with 5-fluorouracil.

Abstract

PURPOSE:

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.

• Authors: P Gwilt, M Tempero, A Kremer, M Connolly, C Ding
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 45 Issue 3 Pg. 247-51 ( 2000) ISSN: 0344-5704 [Print] Germany
• PMID: 10663643 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Adjuvants, Immunologic
• Antimetabolites, Antineoplastic
• Levamisole
• Fluorouracil

Topics

• Adjuvants, Immunologic (pharmacokinetics)
• Administration, Oral
• Aged
• Antimetabolites, Antineoplastic (therapeutic use)
• Colorectal Neoplasms (drug therapy, metabolism)
• Female
• Fluorouracil (therapeutic use)
• Humans
• Levamisole (blood, pharmacokinetics)
• Male
• Metabolic Clearance Rate
• Middle Aged
• Time Factors