The effect of food on oral melphalan absorption

Fifteen patients receiving oral melphalan (4.2-5.3 mg/m2) for a variety of neoplastic disorders were studied. Ten patients received the drug on separate occasions, with and without a standardized breakfast. Eight of these patients also received an IV bolus dose (5 mg/m2) to determine bioavailability...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 1986-03, Vol.16 (2), p.194-197
Main Authors: REECE, P. A, KOTASEK, D, MORRIS, R. G, DALE, B. M, SAGE, R. E
Format: Article
Language:English
Subjects:
Absorption
Administration, Oral
Aged
Antineoplastic agents
Biological and medical sciences
Biological Availability
Chemotherapy
Chromatography, High Pressure Liquid
Fasting
Female
Food
Humans
Injections, Intravenous
Kinetics
Male
Medical sciences
Melphalan - administration & dosage
Melphalan - blood
Melphalan - metabolism
Melphalan - therapeutic use
Middle Aged
Neoplasms - drug therapy
Pharmacology. Drug treatments
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Summary:Fifteen patients receiving oral melphalan (4.2-5.3 mg/m2) for a variety of neoplastic disorders were studied. Ten patients received the drug on separate occasions, with and without a standardized breakfast. Eight of these patients also received an IV bolus dose (5 mg/m2) to determine bioavailability. Serial melphalan plasma samples were taken over 5 h after administration and assayed by high-performance liquid chromatography. The median area under the curve (AUC) when taken fasting was 179 (range 95-336) ng X h X ml-1, and when taken with food, 122 (47-227) ng X h X ml-1, the median reduction being 39% (P less than 0.01). In one patient, who died before completing the study, the drug was not detectable at all after being taken with food. In the eight patients who were also given IV melphalan, the median terminal melphalan half-life (57 min, range 38-71) was no different from its oral half-life [55 (27-104) min fasting; 55 (30-72) min with food] (P greater than 0.1). In these patients bioavailability was 85% (26-96)% when the drug was taken fasting and 58% (7-99)% when taken with food (P less than 0.025). Median clearance following IV administration was 362 ml/min/m2 (range 104-694). It was found that the melphalan level in a single plasma sample drawn 1.5 h after administration was highly predictive of oral melphalan AUC (rs = 0.915, P less than 0.1). This study suggests that to ensure optimum absorption of the drug, melphalan should not be taken with food.
ISSN:0344-5704
1432-0843
DOI:10.1007/bf00256176