title: What do we know about steroids metabolism and 'PK/PD approach' in AKI and CKD especially while on RRT--current status in 2014.
abstract: The knowledge on PK behavior of steroid drugs such as prednisolone or prednisone has indeed been expanding but at a rather slow pace. First, convenient, rapid, and specific determination of plasma levels of these steroids was largely indebted to the breakthrough of high performance liquid chromatography (HPLC). Second, prednisolone is non-linearly protein-bound. Since unbound prednisolone is the biologically active compound, only the measurement of this free fraction in plasma is relevant. Third, the short half-life of prednisolone precludes to reach steady-state levels and requires determination of the area under the concentration-time curve. Fourth, prednisolone and prednisone are mutually convertible. Intravenous prednisolone, however, is administered as a pro-drug ester, which renders comparison and interpretation of reported PK data of both agents unreliable. A poignant lack of awareness and knowledge regarding catabolism, clearance mechanisms, and elimination route of steroids fuels the ongoing controversy that surrounds adjunctive corticosteroid therapy in patients with chronic or acute inflammatory disease. This particular patient population is also more prone to develop early and significant kidney dysfunction, necessitating extra-renal support. A better understanding of steroid PK/PD, preferentially guided by HPLC measurement of plasma steroid concentrations, likely will have direct clinical implications, for instance by adapting steroid doses in IHD or implementing higher dose regimens during CRRT.
authors.affiliation: ICU Department, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Honoré
authors.forename: Rita
authors.initials: R
authors.lastname: Jacobs
authors.forename: Elisabeth
authors.initials: E
authors.lastname: De Waele
authors.forename: Jouke
authors.initials: J
authors.lastname: De Regt
authors.forename: Thomas
authors.initials: T
authors.lastname: Rose
authors.forename: Viola
authors.initials: V
authors.lastname: Van Gorp
authors.forename: Olivier
authors.initials: O
authors.lastname: Joannes-Boyau
authors.forename: Willem
authors.initials: W
authors.lastname: Boer
authors.forename: Herbert D
authors.initials: HD
authors.lastname: Spapen
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000503:physiopathology / Q000628:therapy; D001798:Blood Proteins / Q000378:metabolism; D003907:Dexamethasone / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D054796:Drug Dosage Calculations; D006801:Humans; D006854:Hydrocortisone / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D008775:Methylprednisolone / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D011241:Prednisone / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D011485:Protein Binding; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000503:physiopathology / Q000628:therapy; D017582:Renal Replacement Therapy
chemical_list: D001798:Blood Proteins; D003907:Dexamethasone; D011241:Prednisone; D006854:Hydrocortisone; D008775:Methylprednisolone