Prolongation of ifosfamide elimination half-life in obese patients due to altered drug distribution

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Abstract
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. >20% over their ideal body weight). The terminal elimination half-life (t1/2 β) 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< 0.05). This prolongation of the elimination half-life was due to an increased volume of distribution (Vdβ) in the obese group (42.81 l, range 35.49–51.90 l) vs 33.70 l range (17.76–50.62 l) (Pdβ correlated with both TBW and the percentage of IBW, but not with IBW itself. When Vdβ 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.