Area-under-the-curve monitoring of prednisolone for dose optimization in a stable renal transplant population

Potter, JM, McWhinney, BC, Sampson, L and Hickman, PE (2004) Area-under-the-curve monitoring of prednisolone for dose optimization in a stable renal transplant population. Therapeutic Drug Monitoring, 26 4: 408-414. doi:10.1097/00007691-200408000-00011


Author Potter, JM
McWhinney, BC
Sampson, L
Hickman, PE
Title Area-under-the-curve monitoring of prednisolone for dose optimization in a stable renal transplant population
Journal name Therapeutic Drug Monitoring   Check publisher's open access policy
ISSN 0163-4356
Publication date 2004-01-01
Sub-type Article (original research)
DOI 10.1097/00007691-200408000-00011
Volume 26
Issue 4
Start page 408
End page 414
Total pages 7
Editor G. Koren
M. Oellerich
Place of publication USA
Publisher Lippincott Williams & Wilkins
Collection year 2004
Language eng
Subject CX
730306 Evaluation of health outcomes
730305 Diagnostic methods
320503 Clinical Pharmacology and Therapeutics
Abstract Background: Renal transplant recipients were noted to appear cushingoid while on low doses of steroid as part of a triple therapy immunosuppression of cyclosporin A (CsA), prednisolone, and azathioprine. Methods: The study group comprised adult renal transplant recipients with stable graft function who had received their renal allograft a minimum of 1 year previously (43 studies undertaken in 22 men and 20 women) with median daily prednisone dose of 7 mg (range 3-10). The control group was healthy nontransplant subjects [median dose 10 mg (10-30)]. Prednisolone bioavailability was measured using a limited 6-hour area under the curve (AUC), with prednisolone measured using specific HPLC assay. Results: The median prednisolone AUC/mg dose for all transplant recipients was significantly greater than the control group by approximately 50% (316 nmol(.)h/L/mg prednisolone versus 218). AUC was significantly higher in female recipients (median 415 versus 297 for men) and in recipients receiving cyclospotin (348 versus 285). The highest AUC was in women on estrogen supplements who were receiving cyclosporin (median 595). A significantly higher proportion of patients on triple therapy had steroid side effects compared with those on steroid and azathioprine (17/27 versus 4/15), more women than men had side effects (14/16 versus 7/22), and the AUC/mg prednisone was greater in those with side effects than without (median 377 versus 288 nmol-h/L/mg). Discussion: The results are consistent with the hypothesis that CsA increases the bioavailability of prednisolone, most likely through inhibition of beta-glycoprotein. The increased exposure to steroid increased the side-effect profile of steroids in the majority of patients. Because the major contributor to AUC is the maximum postdose concentration, it may be possible to use single-point monitoring (2 hours postdose) for routine clinical studies.
Keyword Medical Laboratory Technology
Pharmacology & Pharmacy
Toxicology
Therapeutic Drug Monitoring (tdm)
Prednisolone
Area Under The Curve (auc)
Cushing's Syndrome
Transplantation
P-glycoprotein
Cyclosporine-a
Pharmacokinetics
Glucocorticoids
Dexamethasone
Disposition
Recipients
Cortisol
Kidney
Users
Q-Index Code CX

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Wed, 15 Aug 2007, 15:11:33 EST