Determination of optimal cholecalciferol treatment in renal transplant recipients using a population pharmacokinetic approach

Purpose No information on optimal cholecalciferol dosing in kidney transplant patients is currently available because the time-course of serum 25-hydroxy vitamin D [25(OH)D] concentration has never been investigated. The aim of this study was to investigate 25(OH)D pharmacokinetics in renal transplant recipients and to determine the optimal dosage scheme allowing 25(OH)D concentrations to be maintained between 30-80 ng/mL during the first year post-transplantation. Methods Four months after renal transplantation, 49 patients received four oral doses of 100,000 IU cholecalciferol every 2 weeks (intensive phase), then every 2 months until 1 year after transplantation (maintenance phase). A control group of 47 transplanted patients was not supplemented but underwent blood sampling. In the treated group, 74 samples were collected before the first cholecalciferol administration and 119 thereafter. Two blood samples per patient were collected in the control group. Serum 25(OH)D concentrations were analyzed using a population approach. The turnover of 25(OH)D was modeled using a one-compartment-model with first-order formation and elimination and basal concentration. Results The mean population parameter estimates and the associated between-subject variability were: formation rate constant (k(f)), 0.11 day(-1); clearance (CL/F), 2.5 L/day (0.42); central volume of distribution (V-C/F), 237 L; basal concentration (C-0), 12.82 ng/mL (0.41). Based on these values, in order to maintain 25(OH)D concentrations between 30 and 80 ng/mL, cholecalciferol dosing should be six successive administrations of 100,000 IU at 2-week intervals, followed by 100,000 IU once a month until the end of the first year. Conclusions We present here the first pharmacokinetic model describing the time-course of 25(OH)D. We propose an optimal and practical scheme for the treatment of vitamin D insufficiency after renal transplantation. Taking into account the numerous effects of vitamin D on health, this scheme could help clinicians improve the care of kidney recipients.