P Gwilt1, M Tempero, A Kremer, M Connolly, C Ding. 1. UNMC/Eppley Cancer Center Core Pharmacokinetics Laboratory, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198-6025, USA.
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.
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 cancerpatients. 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: Oliver Kudlacek; Tina Hofmaier; Anton Luf; Felix P Mayer; Thomas Stockner; Constanze Nagy; Marion Holy; Michael Freissmuth; Rainer Schmid; Harald H Sitte Journal: J Chem Neuroanat Date: 2017-06-12 Impact factor: 3.097
Authors: Richard J Maude; Kamolrat Silamut; Katherine Plewes; Prakaykaew Charunwatthana; May Ho; M Abul Faiz; Ridwanur Rahman; Md Amir Hossain; Mahtab U Hassan; Emran Bin Yunus; Gofranul Hoque; Faridul Islam; Aniruddha Ghose; Josh Hanson; Joel Schlatter; Rachel Lacey; Alison Eastaugh; Joel Tarning; Sue J Lee; Nicholas J White; Kesinee Chotivanich; Nicholas P J Day; Arjen M Dondorp Journal: J Infect Dis Date: 2013-08-13 Impact factor: 5.226
Authors: Tina Hofmaier; Anton Luf; Amir Seddik; Thomas Stockner; Marion Holy; Michael Freissmuth; Gerhard F Ecker; Rainer Schmid; Harald H Sitte; Oliver Kudlacek Journal: Neurochem Int Date: 2013-12-01 Impact factor: 4.297