Variability in the pharmacokinetics of epirubicin: a population analysis.
Population pharmacokinetic analysis of the anticancer agent epirubicin was carried out using the program NONMEM. Data were available from 36 patients aged 20-73 years, of whom 23 were women. All subjects exhibited normal liver and renal function. Epirubicin was given as a short-term i.v. infusion over the dose range of 25-100 mg/m2, and an average of 11 plasma samples/subject were taken for a period of up to 72 h after each dose. A Two compartment model was fitted to the data, characterised by the parameters clearance, volume of the central compartment, alpha and beta. Clearance was tested as a linear function of various demographic and/or biochemical features. A significant proportion of the variability in clearance could be attributed to sex, and also to age in women. For example, a 25-year-old man would display an average clearance of 95 l/h, whereas a 70-year-old woman would exhibit an average clearance of 64 l/h. Such differences in clearance might be important in the selection of epirubicin dose regimens.
Wade
J R
JR
Department of Medicine and Therapeutics, University of Glasgow, Gardiner Institute, Western Infirmary, UK.
Kelman
A W
AW
Kerr
D J
DJ
Robert
J
J
Whiting
B
B
D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood / Q000187:drug effects; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D015251:Epirubicin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006689:Hodgkin Disease / Q000097:blood / Q000188:drug therapy; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012509:Sarcoma / Q000097:blood / Q000188:drug therapy; D012727:Sex Characteristics; D013997:Time Factors
D015251:Epirubicin