Prolongation of ifosfamide elimination half-life in obese patients due to altered drug distribution.
The pharmacokinetics of intravenous ifosfamide were determined in 16 patients with carcinoma of the bronchus. In all 25% (4) of these patients were obese (i.e. greater than 20% over their ideal body weight). The terminal elimination half-life (t1/2 beta) was found to be higher in the obese group than in the control group (6.36 h, range 5.77-7.45 h) vs 4.95 h, range 1.82-6.48 h) (P less than 0.05). This prolongation of the elimination half-life was due to an increased volume of distribution (Vd beta) in the obese group (42.81 1, range 35.49-51.90 l) vs 33.70 l range (17.76-50.62 l) (P less than 0.05). There was therefore no significant difference in total plasma clearance between the obese and normal groups. No correlation of ifosfamide plasma half-life was observed with total body weight (TBW) or ideal body weight (IBW). However, a significant positive correlation was observed between the percentage of IBW and plasma half-life. A strong positive correlation was observed between IBW and the plasma clearance of ifosfamide. The Vd beta correlated with both TBW and the percentage of IBW, but not with IBW itself. When Vd beta was normalised for IBW, there was a strong positive correlation with the percentage of IBW, suggesting that ifosfamide distribution into the TBW is higher than that into the IBW.
Lind
M J
MJ
CRC Department of Medical Oncology, Christie Hospital and Holt Radium Institute, Manchester, U.K.
Margison
J M
JM
Cerny
T
T
Thatcher
N
N
Wilkinson
P M
PM
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy; D015080:Mesna / Q000008:administration & dosage; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
D015080:Mesna; D007069:Ifosfamide