Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2014 Publisher: Aspen Pharma Trading Limited, 3016 Lake Drive, Citywest Business Campus, Dublin 24, Ireland
Melphalan is a bifunctional alkylating agent. Formation of carbonium intermediates from each of the two bis-2-chlorethyl groups enables alkylation through covalent binding with the 7-nitrogen of guanine on DNA, cross-linking two DNA strands and thereby preventing cell replication.
The absorption of oral melphalan is highly variable with respect to both the time to first appearance of the drug in plasma and peak plasma concentration.
In studies of the absolute bioavailability of melphalan the mean absolute bioavailability ranged from 56 to 85%.
Intravenous administration can be used to avoid variability in absorption associated with myeloablative treatment.
In a study of 18 patients administered melphalan 0.2 to 0.25 mg/kg bodyweight orally, a maximum plasma concentration (range 87 to 350 nanograms/ml) was reached within 0.5 to 2.0 h.
The administration of melphalan tablets immediately after food delayed the time to achieving peak plasma concentrations and reduced the area under the plasma concentration-time curves by between 39 and 45%.
Melphalan displays limited penetration of the blood-brain barrier. Several investigators have sampled cerebrospinal fluid and found no measurable drug. Low concentrations (~10% of that in plasma) were observed in a single high-dose study in children.
In 13 patients given oral melphalan at 0.6 mg/kg bodyweight, the plasma mean terminal elimination half-life was 90 ± 57 min with 11% of the drug being recovered in the urine over 24 h.
In 18 patients administered melphalan 0.2 to 0.25 mg/kg bodyweight orally, the mean elimination half-life was 1.12 ± 0.15 h.
Melphalan clearance may be decreased in renal impairment (see Dosage and Administration – Renal impairment and Warnings and Precautions – Renal impairment).
No correlation has been shown between age and melphalan clearance or with melphalan terminal elimination half-life (see Dosage and Administration).
There are no preclinical data of relevance to the prescriber, which are additional to that in other sections of the SmPC.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
