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

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Clinical Transplantation

Volume 22 Issue 1 Page 68-75, January/February 2008

To cite this article: M Kovarik, Federico Villamil, Alejandra Otero, Levy, Lynch, Umberto Cillo, Lutz Fischer, Björn Nashan, Steve Pollard, Luciano De Carlis (2008) Cyclosporine pharmacokinetics and blood pressure responses after conversion to once-daily dosing in maintenance liver transplant patients Clinical Transplantation 22 (1), 68–75. doi:10.1111/j.1399-0012.2007.00747.x

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

M. KovarikaaNovartis Pharmaceuticals, Basel, Switzerland, Federico VillamilbbFundacion Favaloro, Buenos Aires, Argentina, Alejandra OteroccHospital Canalejo, La Coruna, Spain, LevyddToronto General Hospital, Toronto, Canada, LyncheePrincess andra Hospital, Brisbane, Australia, Umberto CilloffUniversity of Padua, Padua, Italy, Lutz FischerggTransplantationszentrum, Hamburg, Germany, Björn NashanhhDalhousie University, Halifax, Nova Scotia, Canada, Steve PollardiiAbdominal and Transplant Services, Leeds, UK and Luciano De CarlisjjAzienda Ospedaliera Niguarda Ca Grande, Milan, Italy

aNovartis Pharmaceuticals, Basel, Switzerland, bFundacion Favaloro, Buenos Aires, Argentina, cHospital Canalejo, La Coruna, Spain, dToronto General Hospital, Toronto, Canada, ePrincess andra Hospital, Brisbane, Australia, fUniversity of Padua, Padua, Italy, gTransplantationszentrum, Hamburg, Germany, hDalhousie University, Halifax, Nova Scotia, Canada, iAbdominal and Transplant Services, Leeds, UK and jAzienda Ospedaliera Niguarda Ca Grande, Milan, Italy

Corresponding author: Kovarik, Novartis Pharmaceuticals, Building WSJ103.426, 4002 Basel, Switzerland.Tel.: +41 ; fax: +41 ;e-mail: john.kovarik@...

Study sponsored by Novartis Pharmaceuticals

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: © Blackwell Munksgaard, 2007

Abstract

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.