Pharmacokinetics of rapamycin.

Based on the present findings, a number of preliminary 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; (b) the drug has a relatively long half-life in both humans and animals with 24-hour trough concentrations being within the analytical range of HPLC when immunosuppressive doses are administered; (c) the drug exhibits a proportionality between trough concentrations and dose; (d) trough concentrations of the drug appear to be related to immunosuppressive efficacy and drug-related side effects. The studies described here should provide a basis for the establishment of therapeutic monitoring protocols for RAPA.