BACKGROUND: Glucocorticoids represent a cornerstone in the immunosuppressive therapy after solid organ transplantation. Interconversion between active and inactive states of glucocorticoids (ie, prednisolone and prednisone) is catalyzed by the enzymes 11β-hydroxysteroid dehydrogenases 1 and 2. MATERIALS: This study investigated the pharmacokinetics of prednisolone and prednisone in 16 liver transplant recipients. Blood samples were collected in four 12-hour dosing intervals during the first 3 weeks posttransplant, including samples drawn at 13 time points. RESULTS: Area under the time-concentration curve of prednisolone was 3-13 μg·h·mL·mg·kg with maximum concentrations (Cmax) between 0.37 and 2.5 μg·mL·mg·kg and trough concentrations (C0) between 0.13 and 1.1 μg·mL·mg·kg. The elimination half-lives were 1.9-10.3 hours. Apparent volume of distribution (VD/F) and apparent clearance (Cl/F) were 23-159 L and 4.7-28.7 L/h, respectively. CONCLUSIONS: This study demonstrated large intraindividual and interindividual variabilities in glucocorticoid pharmacokinetics. The results suggest that current prednisolone dosing early after liver transplantation might be too high, in particular when coadministered with methylprednisolone. These findings indicate a potential for improvement by personalized dosing of glucocorticoids in organ transplantation.
BACKGROUND: Glucocorticoids represent a cornerstone in the immunosuppressive therapy after solid organ transplantation. Interconversion between active and inactive states of glucocorticoids (ie, prednisolone and prednisone) is catalyzed by the enzymes 11β-hydroxysteroid dehydrogenases 1 and 2. MATERIALS: This study investigated the pharmacokinetics of prednisolone and prednisone in 16 liver transplant recipients. Blood samples were collected in four 12-hour dosing intervals during the first 3 weeks posttransplant, including samples drawn at 13 time points. RESULTS: Area under the time-concentration curve of prednisolone was 3-13 μg·h·mL·mg·kg with maximum concentrations (Cmax) between 0.37 and 2.5 μg·mL·mg·kg and trough concentrations (C0) between 0.13 and 1.1 μg·mL·mg·kg. The elimination half-lives were 1.9-10.3 hours. Apparent volume of distribution (VD/F) and apparent clearance (Cl/F) were 23-159 L and 4.7-28.7 L/h, respectively. CONCLUSIONS: This study demonstrated large intraindividual and interindividual variabilities in glucocorticoid pharmacokinetics. The results suggest that current prednisolone dosing early after liver transplantation might be too high, in particular when coadministered with methylprednisolone. These findings indicate a potential for improvement by personalized dosing of glucocorticoids in organ transplantation.
Authors: Azrin N Abd Rahman; Susan E Tett; Halim A Abdul Gafor; Brett C McWhinney; Christine E Staatz Journal: Br J Clin Pharmacol Date: 2015-07-02 Impact factor: 4.335
Authors: Felix Krenzien; Abdallah ElKhal; Markus Quante; Hector Rodriguez Cetina Biefer; Uehara Hirofumi; Steven Gabardi; Stefan G Tullius Journal: Transplantation Date: 2015-11 Impact factor: 4.939