Cyclosporine pharmacokinetics and blood pressure responses after conversion to once-daily dosing in maintenance liver transplant patients

• Published in: Clinical transplantation Vol. 22; no. 1; pp. 68 - 75
• Main Authors: Kovarik, John M, Villamil, Federico, Otero, Alejandra, Levy, Gary, Lynch, Stephen, Cillo, Umberto, Fischer, Lutz, Nashan, Björn, Pollard, Steve, Carlis, Luciano De
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2008; Blackwell
• Subjects: Area Under Curve; Biological and medical sciences; blood pressure; Blood Pressure - drug effects; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm - physiology; cyclosporine; Cyclosporine - administration & dosage; Cyclosporine - pharmacokinetics; Dose-Response Relationship, Drug; dosing; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - pharmacokinetics; Liver Transplantation - immunology; Liver Transplantation - physiology; Male; Medical sciences; Middle Aged; pharmacokinetics; Pilot Projects; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tissue, organ and graft immunology; Human; cyclosporine; Digestive system; Liver; Patient; Transplantation; Maintenance; Homotransplantation; dosing; Conversion; Posology; Medicine; Response; Drug conversion; Treatment; Surgery; Graft; Arterial pressure; Ciclosporin; Blood pressure; Hemodynamics; Immunosuppressive agent; Daily dose; Pharmacokinetics
• ISSN: 0902-0063; 1399-0012
• DOI: 10.1111/j.1399-0012.2007.00747.x

:  In this six‐month randomized multicenter trial, we characterized cyclosporine pharmacokinetics and blood pressure profiles in maintenance liver transplant patients converting from twice‐daily to once‐daily cyclosporine dosing. A total of 60 patients were randomized as follows: group A (n = 14) maintained twice‐daily dosing; group B (n = 24) converted to once‐daily dosing at the same total daily dose as pre‐conversion; and group C (n = 22) was treated the same as group B but with a 25% reduction in dose and C2 at two to three wk post‐conversion. After conversion to once‐daily dosing in groups B and C, trough blood levels (C0) did not change; whereas, C2 nearly doubled. The total daily area under the concentration–time curve AUC(0–24) increased by 29%. After the dose reduction in group C, the AUC(0–24) was similar to the pre‐conversion value. Hence, a 25–30% dose reduction can be considered after conversion to once‐daily dosing. In the study observation period in weeks 4–15, the median (25–75 percentile) C2 was 568 (469–750) ng/mL for group A; 1055 (840–1224) ng/mL for group B; and 764 (575–959) ng/mL for group C. Conversion to once‐daily dosing was associated with a decrease in nighttime mean arterial blood pressure.