Bd. Kahan et al., CHALLENGES IN CYCLOSPORINE THERAPY - THE ROLE OF THERAPEUTIC MONITORING BY AREA-UNDER-THE-CURVE MONITORING, Therapeutic drug monitoring, 17(6), 1995, pp. 621-624
Cyclosporine has revolutionized the practice of transplantation, but i
ts clinical application has been beclouded by a narrow therapeutic win
dow between immunosuppressive and nephrotoxic concentrations. Marked i
ntra-and interindividual pharmacokinetic differences preclude the use
of routine dosing regimens. For example, at the intraindividual level,
cyclosporine absorption improves during the first 90 days after insti
tution of therapy. A wide range of demographic factors, namely, age, r
ace, and concomitant drug therapy, as well as individual-specific fact
ors produce unique pharmacokinetic behaviors in any given patient. We
introduced a pharmacokinetic strategy for cyclosporine administration
almost 10 years ago based on the observation that the best estimate of
drug exposure was the area under the concentration-time kinetic curve
(AUC) not the trough level. Early studies documented the relation bet
ween AUC and the incidence of acute rejection. Subsequent studies reve
aled that not only is the AUC an important predictor, but so is the co
nsistency of drug absorption over time; namely, patients with variatio
ns >25% among AUC determinations display an increased risk of chronic
rejection episodes. Therefore therapeutic drug monitoring plays an imp
ortant role in the optimal care of patients under cyclosporine therapy
.