High-dose melphalan dosage adjustment: possibility of using a test-dose.
Previous pharmacokinetic studies of i.v. high-dose melphalan (HDM) have demonstrated large interindividual variations in the pharmacokinetic parameters. We therefore studied the possibility of using a test dose of the drug to determine the level of a subsequent therapeutic dose. This study was undertaken to establish whether the pharmacokinetics of melphalan were linear and reproducible within the same patient and determine whether a linear extrapolation could be carried out from the test dose. The first eight patients were studied on two occasions separated by 2 hours (repeatability stage). Although reasonable evidence for linear pharmacokinetics was obtained from these patients, the data suggested a number of factors that might have introduced errors. Therefore, the second group of ten patients were treated on a slightly different protocol on two occasions 24 h apart (linearity stage). The ratios of the two doses ranged from 1 to 8 (repeatability stage) and from 2.6 to 10 (linearity stage). During both stages there was a good correlation between the AUC measured for the second infusion and that predicted from the first (r = 0.929 and r = 0.943, respectively). We conclude that a test dose can be used to determine the subsequent dose of melphalan necessary to produce a desired AUC.
Tranchand
B
B
Centre Léon Bérard, Lyon, France.
Ploin
Y D
YD
Minuit
M P
MP
Sapet
C
C
Biron
P
P
Philip
T
T
Ardiet
C
C
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*
D005665:Furosemide; D008558:Melphalan