Melphalan pharmacokinetics

Ehrsson H, Eksborg S, Wallin I, Osterborg A, MeUstedt H. Oral melphalan pharmacokinetics influence of interferon-induced fever. Clin Fharmacol Ther 1990 47(l) 86-90. 

A study in 8 patients with multiple myeloma or monoclonal gammopathy showed that pretreatment with cimetidine 1 g daily for 6 days reduced the bioavailability of a 10-mg oral dose of melphalan by 30%. The melphalan half-life was reduced from 1.94 to 1.57 hours. The interindividual variation in melphalan pharmacokinetics was high. Note that, because of the variability in melphalan absorption, the dose of oral melphalan is usually cautiously increased until myelosuppression is seen, to ensure therapeutic levels. Therefore, this modest interaction with cimetidine is unlikely to have many clinical consequences. 

This approach has been implemented in studies of some anticancer drugs. One example is the pharmacokinetically guided administration of melphalan performed in patients with advanced ovarian adenocarcinoma (49). The schedule involved a fixed dose on day 1 (7.9 mg) followed by a second dose on day 2, calculated on... 

D. Y. Ploin, B. Tranchand, J. P. Guastalla, P. Rebattu, F. Chauvin, M. Clavel, and C. Ardiet, Pharmacokinetically guided dosing for intravenous melphalan a pilot study in patients with advanced ovarian adenocarcinoma. Ear J Cancer 28A 1311-1315 (1992). 

In a study intravenous zoledronic acid 4 mg every 4 weeks with alternate day prednisolone was given with or without thalidomide 200 mg daily for up to 1 year. The zoledronic acid pharmacokinetics were not affected by thalidomide and based on renal function no clinically adverse interaction occurred during concurrent use. The subjects in this study were patients with multiple myeloma with no disease progression 6 weeks after autologous stem-cell transplantation and conditioning with melphalan. ... 

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