Area under the curve monitoring of cyclosporine therapy: the early posttransplant period

• Published in: Therapeutic drug monitoring Vol. 13; no. 2; p. 89
• Main Authors: Grevel, J, Kahan, B D
• Format: Journal Article
• Language: English
• Published: United States 01.03.1991
• Subjects: Administration, Oral; Adult; Cyclosporins - administration & dosage; Cyclosporins - pharmacokinetics; Cyclosporins - therapeutic use; Humans; Infusions, Intravenous; Intestinal Absorption; Kidney Transplantation; Postoperative Period; Radioimmunoassay
• ISSN: 0163-4356; 1536-3694
• DOI: 10.1097/00007691-199103000-00001

The impact of a new monitoring strategy on whole blood concentrations of cyclosporine measured by a specific monoclonal radioimmunoassay was investigated in a group of 37 renal transplant patients. Before transplantation, the patients received a standard intravenous (i.v.) and oral (p.o.) test dose of cyclosporine to calculate their individual i.v. and p.o. starting dose rates to achieve a certain target steady-state cyclosporine concentration. After transplantation, the designated i.v. dose rate was continuously infused for 2 days, at which time the steady-state concentration was measured. Then, the designated oral dose for 24 h was administered while the infusion was continued at an unaltered rate. The oral absorption of cyclosporine was documented by blood samples over the following 8 h. If necessary, this overlap of i.v. and p.o. dosing was repeated until blood concentrations of cyclosporine rose at least 700 ng/ml over the steady-state concentration. By that time, the infusion was stopped and oral dosing continued. Individualized infusions led to steady-state concentrations within a range that did not exceed 1.1 times the median concentration of 472 ng/ml. Standard infusion rates in the past produced a much wider range of steady-state concentrations (9.6 times the median). Individualized infusions reached the target steady-state concentration with a significant positive bias of 17% (SEM = +/- 32%, range of -36 to +105%). Individualized oral doses reached the target average steady-state concentration (calculated by dividing the area under the concentration-time curve by the dosing interval) with an inferior precision (median = 2.6%, range of -54 to +130%) but without a positive or negative bias.