Pharmacokinetics and pharmacodynamics of mycophenolic acid and its glucuronide early after renal transplantation

Tett, S. E., Atcheson, B. A., Taylor, P. J., Johnson, D. W., Mudge, D. W. and Pillans, P. I. (2004). Pharmacokinetics and pharmacodynamics of mycophenolic acid and its glucuronide early after renal transplantation. In: Warwick P. Anderson, Clinical and Experimental Pharmacology and Physiology: Abstracts of the 8th World Conference on Clinical Pharmacology & Therapeutics. 8th World Conference on Clinical Pharmacology & Therapeutics 2004, Brisbane, Australia, (A104-A104). 1-6 August, 2004. doi:10.1111/j.1440-1681.2004.cep_4027.pdf.x


Author Tett, S. E.
Atcheson, B. A.
Taylor, P. J.
Johnson, D. W.
Mudge, D. W.
Pillans, P. I.
Title of paper Pharmacokinetics and pharmacodynamics of mycophenolic acid and its glucuronide early after renal transplantation
Conference name 8th World Conference on Clinical Pharmacology & Therapeutics 2004
Conference location Brisbane, Australia
Conference dates 1-6 August, 2004
Proceedings title Clinical and Experimental Pharmacology and Physiology: Abstracts of the 8th World Conference on Clinical Pharmacology & Therapeutics   Check publisher's open access policy
Place of Publication Australia
Publisher Blackwell Publishing
Publication Year 2004
Sub-type Published abstract
DOI 10.1111/j.1440-1681.2004.cep_4027.pdf.x
ISSN 0305-1870
Editor Warwick P. Anderson
Volume 31
Issue Supplement 1
Start page A104
End page A104
Total pages 1
Language eng
Formatted Abstract/Summary
The pharmacokinetics of mycophenolic acid and its glucuronide
are complex. 42 renal transplant recipients receiving mycophenolate
mofetil and concomitant cyclosporin (n = 32) or
tacrolimus (n = 10) participated. Blood samples were taken on day
5 post-transplant. Free and total 6- h area under the concentrationtime
curve (AUC0-6) of mycophenolic acid was assessed relative
to clinical outcomes in the first month post-transplant. Kinetic
variability of free and total mycophenolic acid and its glucuronide
was greater in patients on cyclosporin, than tacrolimus cotherapy.
Cyclosporin-treated patients also had significantly lower predose
total mycophenolic acid concentrations than tacrolimus-treated
patients (P = 0.002). Mycophenolic acid free fraction varied
11-fold, from 1.6% to 18.3%, whilst the glucuronide free fraction
varied 3-fold, from 17.4% to 54.1%. Urea and creatinine, but not
bilirubin concentrations correlated positively (r2 > 0.46), whilst
albumin correlated negatively (r2 = – 0.54) with free fraction
of mycophenolic acid and mycophenolic acid glucuronide.
Mycophenolic acid free fraction was 70% higher in patients with
albumin concentrations below 31 g/L. Neither free nor total
mycophenolic acid AUC0-6 was related to rejection (P > 0.07),
however, free AUC0-6 was related to thrombocytopenic,
leukopenic and/or infectious outcomes (P = 0.0043). Significant
alterations in mycophenolic acid/glucuronide protein binding
occur acutely post-transplant and exposure to unbound drug is
related to infections and haematological toxicity.
Subjects EX
320503 Clinical Pharmacology and Therapeutics
730199 Clinical health not specific to particular organs, diseases and conditions
Q-Index Code EX
Additional Notes Posters A51

 
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Created: Thu, 23 Aug 2007, 19:47:47 EST