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.
Yatscoff
R W
RW
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada.
D000818:Animals; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011090:Polyenes / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D020123:Sirolimus; D014181:Transplantation Immunology
D007166:Immunosuppressive Agents; D011090:Polyenes; D020123:Sirolimus