Recent advances in therapeutic monitoring of cyclosporine: Absorption profiling

Abstract

Cyclosporine (CsA) is an important component of many contemporary immunosuppressive regimens. Because of its narrow therapeutic window, therapeutic drug monitoring is essential. However, after almost 2 decades of clinical experience, the optimal monitoring method remains unclear. CsA trough concentration levels (C 0 ) have been widely used for monitoring despite poor correlation with clinical events and drug exposure measured by area under the concentration-time curve. The latter has better correlation with acute rejection and graft survival, but it is expensive, time consuming, and cumbersome. With the introduction of CsA microemulsion formula (CsA-ME), limited sampling methods to estimate drug exposure and measurement of single postdose CsA concentrations have been examined for their potential monitoring role in optimizing CsA use. Absorption profile, which expresses drug exposure during the most variable portion of the pharmacokinetic curve, has emerged as a more effective measure of therapeutic drug monitoring than trough concentrations. The 2-hour postdose concentration is the most practical surrogate for absorption-profile monitoring and will likely replace C 0 for monitoring CsA-ME preparations. We present a summary of pertinent studies in this field.