1. Cyclosporine pharmacokinetics and blood pressure responses after conversion to once-daily dosing in maintenance liver transplant patients.
- Author
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Kovarik JM, Villamil F, Otero A, Levy G, Lynch S, Cillo U, Fischer L, Nashan B, Pollard S, and De Carlis L
- Subjects
- Area Under Curve, Blood Pressure Monitoring, Ambulatory, Circadian Rhythm physiology, Dose-Response Relationship, Drug, Female, Humans, Male, Middle Aged, Pilot Projects, Blood Pressure drug effects, Cyclosporine administration & dosage, Cyclosporine pharmacokinetics, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents pharmacokinetics, Liver Transplantation immunology, Liver Transplantation physiology
- Abstract
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.
- Published
- 2008
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