title: Large within-day variation in cyclosporine absorption: circadian variation or food effect?
abstract: With the recent focus of monitoring cyclosporine (CsA) therapy using measures of CsA absorption, it is important to understand published reports of diurnal variation in CsA exposure. In 10 renal transplant patients, CsA concentrations were measured 0, 1, 2, 3, and 4 h after both the morning and the evening doses and in a repeat session at least 1 wk later. Both area under the curve for the final 4 h after cyclosporine dose and cyclosporine concentrate 2 h after the cyclosporine dose were more than two-fold higher after the morning dose in both sessions. Because the morning levels were collected in a fasted condition and the evening ones in a fed condition, the study was extended to collect evening levels after fasting. The area under the curve for the final 4 h after cyclosporine dose and cyclosporine concentrate 2 h after the cyclosporine dose values observed now were comparable to the morning fasted values. That the large diurnal variation was due to variation in food consumption, as opposed to a biologic circadian rhythm affecting CsA absorption, has significant implications for therapeutic drug monitoring.
authors: Department of Medicine, University of Alabama Medical Center, 1900 University Boulevard, THT 643, Birmingham, AL 35294, USA. macbama@uab.edu
authors: John J
authors: JJ
authors: Curtis
authors: Patsy
authors: P
authors: Jones
authors: Ralph
authors: R
authors: Barbeito
mesh_terms: D000042:Absorption; D000328:Adult; D000368:Aged; D002940:Circadian Rhythm; D016572:Cyclosporine / Q000378:metabolism*; D005260:Female; D005502:Food; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine