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• W2038088215 abstract "Based on the findings above, a number of conclusions can be made regarding the distribution, pharmacokinetics, and therapeutic range investigations with RAPA: (a) the majority of the drug is sequestered in erythrocytes, resulting in whole blood concentrations being considerably higher than plasma concentrations; (b) the drug is metabolized by the same cytochrome P450 3A enzyme involved in the metabolism of CsA and FK506. Metabolites are primarily simple demethylations and hydroxylations with 41-O-demethyl RAPA being the major metabolite both in vivo and in vitro; (c) the drug has a relatively long half-life in both humans and animals with 24-h trough concentrations being within the analytical range of HPLC when immunosuppressive doses are administered; (d) the drug exhibits a degree of proportionality between trough concentrations and dose; (e) a strong correlation exists between area under the concentration-time curve and trough blood concentration at steady state; (f) trough concentrations of the drug appear to be related to immunosuppressive efficacy and drug-related side effects; (g) the nephro- and neurotoxic properties of CsA are not augmented by concurrent treatment with RAPA; and (h) phase IIB trial results have shown a decrease of acute rejection episodes from 40% to < 10% among patients treated with full-dose CsA plus RAPA. The studies described here should provide a basis for the establishment of therapeutic monitoring protocols for RAPA. In addition, new derivatives of RAPA, such as SDZ RAD, designed to overcome formulation problems associated with RAPA, while maintaining similar pharmacokinetics and in vivo activity, show promise as alternatives to RAPA." @default.
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• W2038088215 date "1998-07-01" @default.
• W2038088215 modified "2023-10-17" @default.
• W2038088215 title "Rapamycin: distribution, pharmacokinetics and therapeutic range investigations: an update" @default.
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• W2038088215 doi "https://doi.org/10.1016/s0009-9120(98)00048-4" @default.
• W2038088215 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9721433" @default.
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