Please use this identifier to cite or link to this item: https://hdl.handle.net/10137/12208
Title: Important lack of difference in tacrolimus and mycophenolic acid pharmacokinetics between Aboriginal and Caucasian kidney transplant recipients.
Authors: Barraclough, Katherine A
Metz, David
Staatz, Christine E
Gorham, Gillian
Carroll, Robert
Majoni, Sandawana William
Sajiv, Cherian
Swaminathan, Ramyasuda
Holford, Nick
Citation: This article is protected by copyright. All rights reserved.
Nephrology (Carlton). 2022 Jun 21. doi: 10.1111/nep.14080.
Abstract: AIM: To examine whether differences in tacrolimus and mycophenolic acid (MPA) pharmacokinetics contribute to the poorer kidney transplant outcomes experienced by Aboriginal Australians. METHODS: Concentration-time profiles for tacrolimus and MPA were prospectively collected from 43 kidney transplant recipients: 27 Aboriginal and 16 Caucasian. Apparent clearance (CL/F) and distribution volume (V/F) for each individual were derived from concentration-time profiles combined with population pharmacokinetic priors, with subsequent assessment for between-group difference in pharmacokinetics. In addition, population pharmacokinetic models were developed using the prospective dataset supplemented by previously developed structural models for tacrolimus and MPA. The change in NONMEM objective function was used to assess improvement in goodness of model fit. RESULTS: No differences were found between Aboriginal and Caucasian groups or empirical Bayes estimates, for CL/F or V/F of MPA or tacrolimus. However, a higher prevalence of CYP3A5 expressers (26% compared with 0%) and wider between-subject variability in tacrolimus CL/F (SD=5.00 compared with 3.25 L/h/70kg) were observed in the Aboriginal group, though these differences failed to reach statistical significance (p=0.07 and p=0.08). CONCLUSION: There were no differences in typical tacrolimus or MPA pharmacokinetics between Aboriginal and Caucasian kidney transplant recipients. This means that Bayesian dosing tools developed to optimise tacrolimus and MPA dosing in Caucasian recipients may be applied to Aboriginal recipients. In turn, this may improve drug exposure and thereby transplant outcomes in this group. Aboriginal recipients appeared to have greater between-subject variability in tacrolimus CL/F and a higher prevalence of CYP3A5 expressers, attributes that have been linked with inferior outcomes.
Click to open Pubmed Article: https://www.ezpdhcs.nt.gov.au/login?url=https://www.ncbi.nlm.nih.gov/pubmed/35727904
Journal title: Nephrology (Carlton, Vic.)
Publication Date: 2022-06-21
Type: Journal Article
URI: https://hdl.handle.net/10137/12208
DOI: 10.1111/nep.14080
Orcid: 0000-0001-9548-2310
0000-0002-4031-2514
Appears in Collections:(a) NT Health Research Collection

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