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Anticancer Research vol. 19, n°1, 837-842. Meeting abstract. Abstract n° 873 - 1999
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Pharmacokinetic modelling of Ifosfamide during continuous infusion over 120 hours at the dose of 6 g/m².
P. Passe, G. Delépine, S. Urien, J.C. Desbois, P. Arnaud. F. Traore, F. Brion, Nicole Delepine
Pharmacokinetic modelling of ifosfamide during continuous infusion over 120 hours at the dose of 6 g/m2 ().
Ifosfamide (IFX) pharmacokinetics (PK) (prodrug and metabolites) is promising to be one of the most important means to adapt doses and obtain better dose intensity in the future. Therefore, we tried to find the best modelling for IFX PK.
We studied IFX PK in 12 patients aged 8-19 years receiving 16 courses of IFX continuously infused over 5 days at a dosage of 6 g/m2 per course. IFX serum concentrations were measured by gas chromatography with thermoionic detection. We applied two monocompartmental PK models to these data: Boddy's model (Cancer Chem Pharmacol; 36:53-60 1995) and Levy's model (J Pharmacol Biopharm; 7:6 1979) that we proposed. They both describe the auto-induction of IFX. PK parameters were estimated by non linear regression. Studied variables were volume of distribution (Vd.), clearance at the beginning of the induction (Cli), clearance extrapolated at infinite (Clf), clearance at 120 hours (C1120), a rate constant (Kc) that relates the clearance variations to time, and lag time that.