Saturable binding of cyclosporin A to erythrocytes: estimation of binding parameters in renal transplant patients and implications for bioavailability assessment.
Cyclosporin (CyA) exhibits saturable binding to erythrocytes. A one-site binding model was fitted to data from renal transplant patients receiving CyA therapy. The average maximum binding capacity is 2560 micrograms CyA/liter of packed erythrocytes; the unbound CyA concentration associated with 50% saturation of the binding site is 67 micrograms/liter. Analysis indicates that whole-blood CyA measurement to monitor drug therapy should be viewed cautiously, particularly when the hematocrit varies considerably. The error in estimating absolute bioavailability at steady state from whole-blood measurements, resulting as a consequence of the saturable binding, has been explored. Although extrapolation to the therapeutic situation, which involves transient drug administration, is difficult, errors of up to 25% are anticipated. When an accurate estimate of bioavailability is required, analysis based on plasma data is proposed. For bioequivalence testing, both blood and plasma CyA data are equally acceptable.
Legg
B
B
Department of Pharmacy, University of Manchester, England.
Rowland
M
M
D001667:Binding, Competitive; D001682:Biological Availability; D003524:Cyclosporins / Q000097:blood* / Q000493:pharmacokinetics; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D016030:Kidney Transplantation
D003524:Cyclosporins