Ifosfamide Barbiturates

BARBITURATES IFOSFAMIDE t rate of biotransformation to 4-hydroxyifbsfamide, the active metabolite, but no change in AUC of 4-hydroxyifosfamide Due to t rate of metabolism and of clearance resulting from induction of CYP3A4 and CYP2D6 Be aware - clinical significance may be minimal or none... 

Evidence suggests that neither the toxicity nor the therapeutic effects of cyclophosphamide and ifosfamide are significantly altered by the concurrent use of barbiturates. However, an isolated report describes a girl taking phenobarbital who developed encephalopathy when given ifosfamide. 

The relationship between the case of encephalopathy and the use of ifosfamide with phenobarbital is not established, but it serves to emphasise the need for particular caution and good monitoring if concurrent use is undertaken. More study is needed. Although barbiturates can cause an increase in the rate of metabolism of cyclophosphamide, this does not appear to alter the AUC and the efficacy of this drug. 

Rifampicin is an inducer of the cytochrome P450 isoenzymes CYP3A4 and CYP2B6, which are involved in the metabolism of cyclophosphamide and ifosfamide (see also Cyclophosphamide or Ifosfamide + Barbiturates , p.623). In the clinical study cited, rifampicin did not have a positive effect on the proportion of ifosfamide undergoing activation. In addition, since rifampicin increased metabolism overall, there is the possibility of decreased efficacy, although this remains to be shown. 

The alteration in the pattern of ifosfamide metabolites suggested that phenytoin had induced the activity of the cytochrome P450 isoenzyme CYP2B6, and to a lesser extent CYP3A4. The pattern of the increase in cyclophosphamide clearance is also consistent with induction of CYP2B and CYP3A. See also Cyclophosphamide or Ifosfamide + Barbiturates , p.623. 

Examples of complete resolutions on a preparative as well on an analytical scale are thalidomide (2), ifosfamide (3), praziquantel (4) mianserin (5) and barbiturates like (6) and (7). 

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