Oral melphalan pharmacokinetics — relation to dose in patients with multiple myeloma
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The pharmacokinetics of melphalan have been studied after oral doses of 5,10 and 20 mg, and 10 mg i.v. Seven patients with multiple myeloma received the drug on 4 consecutive days and the concentration of melphalan was determined by liquid chromatography. Melphalan was rapidly absorbed after p.o. administration. Absorption lag-time was less than 1 h. The median time for attaining the peak concentration was 1.12 h (97% confidence interval: 0.68–1.55), 1.21 h (0.85–1.43) and 1.08 h (0.84–1.29) after doses of 5,10 and 20 mg. The bioavailability showed large interindividual variations, and was not significantly affected by the dose given. There was a significant decrease in bioavailability during the treatment course (P < 0.05). Absorption of melphalan obeys first-order kinetics in the dose interval studied. The results indicate that it might be of benefit to administrate oral melphalan for fewer days than the usually used 4 day regimen, in an attempt to achieve a higher bioavailability.
Key wordsMelphalan Pharmacokinetics Oral administration Chemotherapy Multiple myeloma
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