Cyclosporine Absorption Profiling and Therapeutic Drug Monitoring in Stable Renal Allograft Recipients

OBJECTIVE Therapetic drug monitoring for cyclosporine microemulsion (CsA-ME) is often performed using trough levels (C₀) or levels at 2 h post-dose (C₂). This analysis assessed changes in C₀ and C₂ and their relationship to CsA-ME dose over one year post-transplant in renal transplant patients. METHODS All 92 post-transplant patients in whom C₀ and C₂ were available at month 1, 3, 6, 12 were measured by FPIA. Normalized dose (ND) of CsA-ME, defined as dose per kilogram body weight, was caculated, together with C₀/ND, C₂/ND and C₂/C₀. RESULTS Both C₀/ND and C₂/ND increased between month 1 and 3: C₀/ND increased from 43±15 to 56±20 (ng·mL^-1)/(mg·kg^-1) and C₂/ND increased from 129±62 to 212±80 (ng·mL^-1)/(mg·kg^-1). Between month 3 and 12, C₂/ND remained stable but C₀/ND decreased to 48±15 (ng·mL^-1)/(mg·kg^-1) while the C₂/C₀ ratio increased from 4.5±1.9 to 5.2±2.3, indicating an acceleration of drug elimination. The inter-individual coefficient of variation was higher for C₂/ND than for C₀/ND at month 3 and 12. CONCLUSION CsA-ME clearance accelerates between month 3 and 12 post-transplant, resulting in lower C₀ levels for a given exposure. As a consequence, C₀ monitoring may not progressively underestimate CsA-ME exposure during the first year post-transplant. C₂ monitoring contributes to improve individualized CsA-ME treatment beyond month 3.