Abstract
Background: We have often observed that the blood trough concentration (Ct) of the once-daily, prolonged-release formulation of tacrolimus (Graceptor®; GRC) becomes unstable, and it is difficult to adjust it in the early period after transplantation. Consequently, we compared the relationships between pharmacokinetic parameters and influencing factors in a group of GRC-treated patients compared with those in a group of Prograf® (PRG)-treated patients. Methods: The study included 8 patients who were newly treated with GRC and 44 patients who were newly treated with PRG. We performed 24-hour therapeutic drug monitoring to compare the relationships between pharmacokinetic parameters, including the area under the curve (AUC), the ratio of the area under the trough level (AUTL)/AUC to indicate the relationships among AUCs, peak concentration (Cp), and Ct. The Cp/Ct values, and dose/body weight (UC/ [D/BW]) values reflected bioavailability and the influencing factors; number of days after transplantation and Dose/BW in the GRC-treated and PRG-treated patients. Results: The Cp/Ct values were higher and the AUTL/AUC and AUC corrected by dose/body weight (AUC/[D/BW]) values were lower with a low number of days after transplantation (particularly within 20 days) and a large dose than a high number of days after transplantation and a small dose in the GRC-treated patients. No such associations were observed in the PRG-treated patients. Conclusion: Care is required when using GRC as there is a tendency for Cp to increase owing to rapid absorption within 20 days after transplantation. Blood levels may be unstable and side effects may be more prevalent in some patients. Moreover, the utilization rate is low and the dose is high in such patients; therefore, unstable gastrointestinal function caused by a variety of factors may play a role in the early period after transplantation.
Highlights
The most common regimen following kidney transplantation involves treatment with one of four immunosuppressive agents and has been shown to achieve excellent outcomes
The pharmacokinetics of Graceptor® (GRC TAC QD) differ slightly from those of tacrolimus BID [Prograf®; PRG] as a result of differences in the inactive ingredients included in the capsules
The aim of the present study was to analyze pharmacokinetic parameters to determine the factors leading to unstable Ct in GRC-treated patients in early-phase renal transplantation and compare them to those for PRG-treated patients
Summary
The most common regimen following kidney transplantation involves treatment with one of four immunosuppressive agents (tacrolimus [TAC], mycofenolate mofetil [MMF], basiliximab, and corticosteroid) and has been shown to achieve excellent outcomes. The pharmacokinetics of Graceptor® (GRC TAC QD) differ slightly from those of tacrolimus BID [Prograf®; PRG] as a result of differences in the inactive ingredients included in the capsules. We have often observed that the Ct of GRC becomes unstable over time, making it nearly impossible to titrate the dosage up, and it can be difficult to adjust the dosage in the early period after transplantation. The aim of the present study was to analyze pharmacokinetic parameters to determine the factors leading to unstable Ct in GRC-treated patients in early-phase renal transplantation and compare them to those for PRG-treated patients. We have often observed that the blood trough concentration (Ct) of the once-daily, prolonged-release formulation of tacrolimus (Graceptor®; GRC) becomes unstable, and it is difficult to adjust it in the early period after transplantation. We compared the relationships between pharmacokinetic parameters and influencing factors in a group of GRC-treated patients compared with those in a group of Prograf® (PRG)-treated patients
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