Pharmacokinetics of high-dose intravenous melphalan in patients undergoing peripheral blood hematopoietic progenitor-cell transplantation.
The pharmacokinetics of melphalan following high-dose (140 mg/m2) i.v. administration were determined in 20 patients with advanced malignancies undergoing peripheral blood hematopoietic progenitor-cell transplantation. Melphalan was assayed in plasma by a specific HPLC method with UV detection. Plasma levels of melphalan declined in a biexponential fashion with a mean terminal half-life of 83 minutes (range 52-168 minutes). Estimated peak plasma concentrations ranged from 1.65 to 14.5 micrograms/ml. Plasma levels were lower than the limit of quantitation of the method used (20 ng/ml) 24 hours after drug administration. The average volume of distribution and total clearance were 317 ml/min/m2 (range 127-797 ml/min/m2) and 37.9 l/m2 (range 15.4-108 l/m2), respectively. These parameters are similar to those reported in the literature. A weak correlation was found between total clearance of melphalan and creatinine clearance (p < 0.05). No relationship between the pharmacokinetics of melphalan and myelosuppression and non-hematologic toxicities was recovered. This pharmacokinetic study indicates that on the assumption that there is no more circulating melphalan after seven elimination half-lives, it may be possible to reinfuse autologous PBPC 10-20 hours after melphalan administration.
Pinguet
F
F
Laboratoire d'Onco-Pharmacologie, Centre Régional de Lutte contre le Cancer, Montpellier, France.
Martel
P
P
Fabbro
M
M
Petit
I
I
Canal
P
P
Culine
S
S
Astre
C
C
Bressolle
F
F
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy; D005260:Female; D006207:Half-Life; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007262:Infusions, Intravenous; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy; D012512:Sarcoma, Ewing / Q000097:blood / Q000188:drug therapy
D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan