Cyclosporine pharmacokinetics and blood pressure responses after conversion to once-daily dosing in maintenance liver transplant patients.
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.
Kovarik
John M
JM
Novartis Pharmaceuticals, Basel, Switzerland. john.kovarik@Novartis.com
Villamil
Federico
F
Otero
Alejandra
A
Levy
Gary
G
Lynch
Stephen
S
Cillo
Umberto
U
Fischer
Lutz
L
Nashan
Björn
B
Pollard
Steve
S
De Carlis
Luciano
L
D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D002940:Circadian Rhythm / Q000502:physiology; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016031:Liver Transplantation / Q000276:immunology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
D007166:Immunosuppressive Agents; D016572:Cyclosporine