The potential replacement of HPLC by 125I-RIA for the characterization of cyclosporin A: a bioavailability study after oral administration in healthy human subjects.
A significant overestimation of cyclosporin A (CsA) by a radioimmunoassay using 125I-labeled monoclonal antibody (125I-RIA), compared to the reference HPLC method, has been reported for a limited number of samples from transplant patients. However, the extent of the discrepancy, with respect to bioavailability parameters, has not been examined for the case of the oral administration of a single dose CsA to healthy subjects where a number of factors which might be involved in this overestimation (e.g. under steady state condition and a significant accumulation of CsA metabolites) would be absent. Therefore, the objective of this study was to assess the effect of potential difference manifested by the two analytical procedures, 125I-RIA and HPLC, on the bioavailability analysis of CsA. An oral CsA formulation was administered to 22 healthy male subjects and the blood samples were analysed by both 125I-RIA and HPLC. Significant discrepancies in the estimated CsA concentrations by the two methods (paired t-test, P < 0.001) were found. The difference (bias) increased with increasing concentrations of blood CsA (P < 0.001). However, despite the bias in CsA estimations, the AUC and Cmax, obtained by 125I-RIA and HPLC methods showed only small differences (i.e. 2% for AUC and 7% for Cmax). Thus, our results suggest that the bias of the 125I-RIA vis-a-vis the HPLC method in the estimation of CsA blood levels may not, in practice, affect the bioavailability analysis (e.g. bioequivalence study) of CsA in a situation where a single dose CsA is orally administered to healthy subjects.
Lee
Y J
YJ
Department of Pharmaceutics, College of Pharmacy, Seoul National University, South Korea.
Chung
S J
SJ
Shim
C K
CK
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000032:analysis* / Q000493:pharmacokinetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000032:analysis* / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes; D008297:Male; D011863:Radioimmunoassay; D013810:Therapeutic Equivalency
D007166:Immunosuppressive Agents; D007457:Iodine Radioisotopes; D016572:Cyclosporine