Monitoring changes in cyclosporine dosage by trough level testing

The concept of a narrow therapeutic window has guided the management of transplant recipients on cyclosporine immunosuppression since its inception more than a decade ago. The need to maintain immunosuppression and avoid toxicity imposed the requirement of monitoring cyclosporine levels within a limited range. The use of circulating trough levels to aid in the adjustment of dosage, however, has also led to controversies. Trough levels did not immediately reflect the dose, and circulating drug levels varied even in the absence of dose changes, indicating the role of factors other than the dose. By introducing a time factor or delay between the dose and trough levels, the sequential delay analysis allows a clearer demonstration of the relationship between doses and trough levels. Using dose adjustments as markers, corresponding changes in the trough levels were observed for most markers after a short delay. The existence of a time factor imposes some restrictions on the scheduling of dose changes and trough level tests. Adjustments in dose need to be separated to avoid interference from each other and the frequency of testing after a change increased to assure its detection. Consideration of the delay should aid in the adjustment of doses and provide an initial step in the understanding of other factors in the relationship between the dose and circulating trough levels.