The pharmacokinetics of melphalan during intermittent therapy of multiple myeloma.
During intermittent melphalan-prednisone therapy the area under the plasma concentration-time curve of melphalan increased by an average of 45% after oral or intravenous administration of the drug in myeloma patients during the initial three courses at six-week intervals. The rise in melphalan plasma concentrations could not be referred to an alteration in melphalan elimination, metabolism, erythrocyte/plasma partition ratio, or protein binding. A possible explanation could be that covalent binding sites of melphalan were successively saturated during intermittent treatment, resulting in higher drug concentrations during successive courses of therapy.
Loos
U
U
Department of Internal Medicine, University of Bonn, Federal Republic of Germany.
Musch
E
E
Engel
M
M
Hartlapp
J H
JH
Hügl
E
E
Dengler
H J
HJ
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism; D011241:Prednisone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics
D008558:Melphalan; D011241:Prednisone