title: Oral melphalan pharmacokinetics--relation to dose in patients with multiple myeloma.
abstract: 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 less than 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.
authors.affiliation: Karolinska Pharmacy, Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Ehrsson
authors.forename: S
authors.initials: S
authors.lastname: Eksborg
authors.forename: A
authors.initials: A
authors.lastname: Osterborg
authors.forename: H
authors.initials: H
authors.lastname: Mellstedt
authors.forename: A
authors.initials: A
authors.lastname: Lindfors
mesh_terms: D000284:Administration, Oral; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D008558:Melphalan