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

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

Authors: Kovarik, M1; Villamil, Federico2; Otero, Alejandra3; Levy, 4; Lynch, 5; Cillo, Umberto6; Fischer, Lutz7; Nashan, Björn8; Pollard, Steve9; Carlis, Luciano De10

Source: Clinical Transplantation, Volume 22, Number 1, January/February 2008 , pp. 68-75(8)

Publisher: Blackwell Publishing

Abstract:Kovarik JM, Villamil F, Otero A, Levy G, Lynch S, Cillo U, Fischer L, Nashan B, Pollard S, De Carlis L. Cyclosporine pharmacokinetics and blood pressure responses after conversion to once-daily dosing in maintenance liver transplant patients. Clin Transplant 2007 DOI: 10.1111/j.1399-0012.2007.00747.x © Blackwell Munksgaard, 2007 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.

Keywords: blood pressure; cyclosporine; dosing; pharmacokinetics

Document Type: Research article

DOI: 10.1111/j.1399-0012.2007.00747.x

Affiliations: 1: Novartis Pharmaceuticals, Basel, Switzerland 2: Fundacion Favaloro, Buenos Aires, Argentina 3: Hospital Canalejo, La Coruna, Spain 4: Toronto General Hospital, Toronto, Canada 5: Princess andra Hospital, Brisbane, Australia 6: University of Padua, Padua, Italy 7: Transplantationszentrum, Hamburg, Germany 8: Dalhousie University, Halifax, Nova Scotia, Canada 9: Abdominal and Transplant Services, Leeds, UK 10: Azienda Ospedaliera Niguarda Ca Grande, Milan, Italy