Effect of L-leucine on oral melphalan kinetics in patients
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Melphalan uptake in the intestine has recently been shown to be an energy-dependent process which is affected by metabolic inhibitors. It is therefore theoretically possible that amino acids in food could reduce melphalan absorption by competing for uptake at the sites of absorption in the intestine. Since L-leucine has been shown to be the most potent inhibitor of melphalan transport into cells in vitro, this amino acid was chosen for the present study in patients. Oral melphalan (4.5±0.5 mg/m2) was given to ten fasting patients with and without a 2-g oral dose of L-leucine on separate randomized occasions at least 1 week apart. Melphalan plasma levels were measured by high-performance liquid chromatography (HPLC) for 5-h after dosing. L-Leucine plasma levels were measured by HPLC before and at 1 h after dosing. The area under the curve for melphalan was lower in seven of the patients after L-leucine. Plasma L-leucine levels 1 h after melphalan administration were 15.4±3.7 μg/ml fasting and 35.4±5.2 μg/ml after L-leucine. The results indicate that L-leucine can reduce plasma melphalan levels in some patients, probably through a reduction in absorption of the drug from the gastrointestinal tract. However, the effect, like that of food, is highly variable.
KeywordsLiquid Chromatography Cancer Research Plasma Level Melphalan Gastrointestinal Tract
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- 1.Adair CG, McElnay JC (1986) Studies on the mechanism of gastrointestinal absorption of melphalan and chlorambucil. Cancer Chemother Pharmacol 17:95–98Google Scholar
- 2.Bosanquet AG, Gilby ED (1984) Comparison of the fed and fasting states on the absorption of melphalan in multiple myeloma. Cancer Chemother Pharmacol 12:183–186Google Scholar
- 3.Dufour M, Panasci LC, Germain Jst, Boulet L (1985) Effects of amino acids on the transport and cytotoxicity of melphalan by human bone marrow cells and human tumour cells. Cancer Chemother Pharmacol 15:125–131Google Scholar
- 4.Hill D, Burnworth L, Skea W, Pfeifer R (1982) Quantitative HPLC analysis of plasma amino-acids as orthophthalaldehyde-ethanethiol derivatives. J Liquid Chromatogr 5: 2369–2399Google Scholar
- 5.Reece PA, Kotasek D, Morris RG, Dale BM, Sage RE (1986) The effect of food on oral melphalan absorption. Cancer Chemother Pharmacol 16:194–197Google Scholar
- 6.Silk DBA, Hegarty JE, Fairclough PD, Clark ML (1982) Characterization and nutritional significance of peptide transport in man. Ann Nutr Metab 26:337–352Google Scholar
- 7.Vistica DT (1983) Cellular pharmacokinetics of the phenylalanine mustards. Pharmacol Ther 22:379–405Google Scholar