Circadian variation of cyclosporine A in renal transplanted patients.

BACKGROUND: A problem with the clinical use of cyclosporine A is the wide patient-to-patient variability in blood levels. OBJECTIVE: To evaluate the circadian variation in patients with renal transplant on twice daily dosing in order to evaluate if patients could need a dosage adjustment in diurnal or nocturnal dose. MATERIAL AND METHODS: The circadian variation of oral cyclosporine pharmacokinetics at steady state was evaluated in 20 patients with renal transplant. Drug doses were administered daily at 8 am and at 8 pm and blood samples for cyclosporine levels measurement by radioimmunoassay were taken during the morning treatment and the evening treatment. RESULTS: Differences were found in the minimum steady state concentration between the morning and the evening administration, however no statistical differences were obtained in peak steady state concentration (Cmaxss), time to peak concentration (tmaxss), area under the curve at steady state (AUCss), mean residence time (MRT) and total clearance (Clt/F). CONCLUSIONS: Therapeutic drug monitoring of cyclosporine A is more important than the time administration.