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Estimation of the effect of food on the disposition of oral 5-fluorouracil in combination with eniluracil.
- Source :
-
Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2002 May; Vol. 49 (5), pp. 398-402. Date of Electronic Publication: 2002 Feb 23. - Publication Year :
- 2002
-
Abstract
- Aims: To determine the effect of food on the pharmacokinetics of 5-fluoruracil (5-FU) taken orally with eniluracil and to compare the performance of different pharmacokinetic analysis methods in the detection a potential food-drug interaction.<br />Methods: In a randomized, open-label, two-way crossover study, 12 patients received eniluracil (50 mg, orally) on days 1 and 2 and 5-FU (20 mg/m(2), orally) on day 2 following either a 2-h fast or 20 min after a standard meal. Treatments were separated by 7 days. Timed blood samples were collected during the first two treatment periods and 5-FU concentrations determined by GC/MS. Data were analyzed and pharmacokinetic parameter estimates were obtained using a noncompartmental, two-stage and population analysis methods.<br />Results: In fasted individuals, the clearance/bioavailability of 5-FU was estimated to be 5.6 l/h. The mean absorption lag-time was 0.24 h and was followed by rapid absorption of 5-FU. Administration of 5-FU and eniluracil with food resulted in a decrease in the 5-FU absorption rate constant by 90%. As a result, the peak plasma concentration (C(max)) of 5-FU was decreased by 21% and the time to C(max) was increased 2.9-fold. Clearance of 5-FU, relative bioavailability, and area under the plasma concentration vs time curve (AUC) remained unchanged with coadministration of food. Similar results were obtained using all three data analysis methods.<br />Conclusions: Administration of food with oral 5-FU and eniluracil slowed absorption of 5-FU and decreased 5-FU C(max), but did not effect AUC. Further investigation of the incorporation of population pharmacokinetic approaches in food effect studies is warranted.
- Subjects :
- Aged
Area Under Curve
Cross-Over Studies
Dihydrouracil Dehydrogenase (NADP)
Dose-Response Relationship, Drug
Double-Blind Method
Drug Interactions
Female
Humans
Intestinal Absorption
Male
Middle Aged
Models, Biological
Oxidoreductases antagonists & inhibitors
Population
Therapeutic Equivalency
Antineoplastic Agents pharmacokinetics
Enzyme Inhibitors pharmacology
Fluorouracil pharmacokinetics
Food-Drug Interactions physiology
Uracil analogs & derivatives
Uracil pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0344-5704
- Volume :
- 49
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cancer chemotherapy and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 11976834
- Full Text :
- https://doi.org/10.1007/s00280-002-0431-9