RAPAMYCIN : DISTRIBUTION, PHARMACOKINETICS AND THERAPEUTIC RANGE INVESTIGATIONS : AN UPDATE

摘要: Based on the findings above, a number of conclusions can be made regarding distribution, pharmacokinetics, and therapeutic range investigations with RAPA: (a) majority drug is sequestered in erythrocytes, resulting whole blood concentrations being considerably higher than plasma concentrations; (b) metabolized by same cytochrome P450 3A enzyme involved metabolism CsA FK506. Metabolites are primarily simple demethylations hydroxylations 41-O-demethyl RAPA major metabolite both vivo vitro; (c) has relatively long half-life humans animals 24-h trough within analytical HPLC when immunosuppressive doses administered; (d) exhibits degree proportionality between dose; (e) strong correlation exists area under concentration-time curve concentration at steady state; (f) appear to related efficacy drug-related side effects; (g) nephro- neurotoxic properties not augmented concurrent treatment RAPA; (h) phase IIB trial results have shown decrease acute rejection episodes from 40% < 10% among patients treated full-dose plus RAPA. The studies described here should provide basis for establishment monitoring protocols In addition, new derivatives RAPA, such as SDZ RAD, designed overcome formulation problems associated while maintaining similar pharmacokinetics activity, show promise alternatives