Publié sur :
Journal of Clinical Oncology - Proceedings of ASCO volume 20 page 118a Abstract N°470 - 2001
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Comparison of the induction effect of Ifosfamide in children and adult population during continuous infusion. Consequences of its metabolites.
B. Gourmel, S. Denis, S. Alkallaf, A. Tabbi, Nicole Delepine
Comparison of the Induction Effect of Ifosfamide in Children and Adult Population During Continuous Infusion. Consequences on its Metabolites.
Developmental Therapeutics - Clinical Pharmacology and Immunotherapy / Pharmacology/Pharmacokinetics
28 Children (6-19 yrs) and 11 adults (40-65yrs), suffering from bone and soft tissue sarcoma, were followed during their treatment session by ifosfamide (Ifos.) 3g/m2/d administered by continuous infusion.
Samples were withdrawn each day at T0, T24, T48, T72, T96 and T120. PK analysis was performed on the basis of the Area Under Curve (AUC) for ifos. and metabolites, in each population. AUC0-24, AUC24-48, ... and AUC96-120 were established for each compound.
The percentage of induction was estimated for ifos. as the ratio between the blood levels T24 / T120. The metabolite index (MI) was defined as the ratio of the AUC : metabolite / parent compound. Ifosfamide. A higher induction percentage was observed in children (33.6% | 20.2%) than in adults (20.8% | 15.3%) during the overall infusion of ifosfamide. Variability in ifos. blood levels was commonly observed. More this decrease started at T96 in adults while at T48 in children. 2D Ifosfamide and 3D Ifosfamide.
In parallel the daily estimation of the MI for these metabolites showed a continuous increase during the infusion duration; the same profile shape was observed for each population during the treatment session. For 2D Ifos., the final values in children and adults were respectively 18.6% | 8.7% and 11.6% | 2.6% and In the case of 3D Ifos. 22.9% | 5.0% and 17.4% | 4.5%. 4 OH Ifosfamide. This active metabolite remained the most interesting metabolite to focus on.
The obtained blood levels remained low during the entire infusion. The estimation of the metabolite index confirmed the previously increase of the amount of 4 OH ifos. remaining available for therapeutic effects.
Final values of the MI in children and adults were respectively 2.3% | 0.8% and 2.9% | 1.1%. The induction observed in children and adults highlighted differences. From the comparison of the percentage of induction, children demonstrated a higher induction than in adults: this is retrieved when MI for 2D and 3D ifos are compared.
However, when it comes to 4 OH ifos, the MI for adults remaines higher. This is confirmed by the PK profiles observed for each compounds and patient populations.