Pharmacokinetic characteristics of methylprednisolone in korean renal transplant recipients

Kang, C. M.; Ahn, Jae-Geun; Kahng, Kyoung Won; Kang, Jin Suk; Shin, Il-Shik; Kwak, Jeonghun

doi:10.1016/s0041-1345(99)00556-4

Cited by 2 publications

(1 citation statement)

References 4 publications

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“…1 20 of the drug than blacks, lower clearance rates than whites, and a longer drug half life than both blacks and whites. 26 Data on azathioprine metabolism in different races are somewhat conflicting, with some studies reporting lower 27 and others higher 28 conversion of the drug to inactive metabolites in those of African origin than in Caucasoids. However, racial differences in the pharmacokinetics of the other immunosuppressive agents (tacrolimus, MMF, and cyclosporin) that were used in our patients have been described.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of autoimmune hepatitis in patients who are not of European Caucasoid ethnic origin

Zolfino

Heneghan²,

Norris³

et al. 2002

Gut

100

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Section: Discussionmentioning

confidence: 99%

Characteristics of autoimmune hepatitis in patients who are not of European Caucasoid ethnic origin

Zolfino

Heneghan²,

Norris³

et al. 2002

Gut

100

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Clinical Pharmacokinetics and Pharmacodynamics of Prednisolone and Prednisone in Solid Organ Transplantation

et al. 2012

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Prednisolone and prednisone are integral components of induction and maintenance immunosuppressive regimens in solid organ transplantation. The pharmacokinetics of these agents are extremely complex. Prednisolone is the active drug moiety while prednisone is both a pro-drug and inactive metabolite of prednisolone. Within the dosage range used in transplantation, prednisolone and prednisone exhibit concentration-dependent non-linear pharmacokinetics when parameters are measured with reference to total drug concentration. Dose dependency disappears when free (unbound) prednisolone is measured. Altered organ function, changing biochemistry and use of a number of concomitant medicines in transplantation appear to lead to pharmacokinetic differences in transplant recipients compared with other patient groups. Greater than threefold variability in dose-adjusted exposure to total prednisolone in transplant recipients is evident. Time post-transplant, hepatic and renal dysfunction, patient age, sex, bodyweight, serum albumin concentration, concomitant medication exposure, various disease states and genetic polymorphisms in metabolic enzymes and drug transporters have sometimes been associated with prednisolone pharmacokinetic variability. The clinical impact of corticosteroid therapy on the disposition of ciclosporin, tacrolimus and sirolimus and the impact of different immunosuppressant therapy combinations on prednisolone exposure needs to be further elucidated. Patient response patterns to prednisolone are consistent with delayed and indirect mechanisms of corticosteroid action involving modification of nuclear transcription and protein synthesis. Many adverse effects have been linked with prednisolone and prednisone therapy, but not all of these have been investigated thoroughly in transplant populations. Dyslipidaemia, growth restriction, diabetogenesis, hypertension and cataracts are well studied toxicities. Evidence is less clear for prednisolone-induced osteonecrosis, obesity and hypertriglyceridaemia. There have been some reports of a relationship between prednisolone pharmacokinetics and incidence of acute rejection, Cushing's syndrome and adverse cardiovascular and metabolic events. Dosing of prednisolone and prednisone in transplantation is typically empirical and varies significantly across transplant centres. Currently, authoritative guidelines are conflicting in their opinions regarding corticosteroid avoidance and early discontinuation in adult kidney transplantation. Overall, data suggest the promise of corticosteroid-free immunosuppression in paediatric patients. Further investigation of the pharmacokinetics and pharmacodynamics of prednisolone and prednisone in transplant recipients based on new chromatography assay techniques and free drug measurement, population pharmacokinetic/pharmacodynamic modelling approaches, genetic testing and larger studies in patients on modern day immunosuppressant protocols may lead to better individualization of corticosteroid therapy in the future.

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Pharmacokinetic characteristics of methylprednisolone in korean renal transplant recipients

Cited by 2 publications

References 4 publications

Characteristics of autoimmune hepatitis in patients who are not of European Caucasoid ethnic origin

Characteristics of autoimmune hepatitis in patients who are not of European Caucasoid ethnic origin

Clinical Pharmacokinetics and Pharmacodynamics of Prednisolone and Prednisone in Solid Organ Transplantation

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