Relationship between allograft cyclosporin concentrations and P-glycoprotein expression in the 1st month following renal transplantation.
ATP Binding Cassette Transporter, Subfamily B
/ analysis
Adolescent
Adult
Aged
Allografts
/ chemistry
Biopsy
Calcineurin Inhibitors
/ administration & dosage
Cyclosporine
/ administration & dosage
Dose-Response Relationship, Drug
Female
Graft Rejection
/ blood
Humans
Kidney
/ chemistry
Kidney Transplantation
/ adverse effects
Male
Middle Aged
Transplantation, Homologous
/ adverse effects
Young Adult
P-glycoprotein
allograft concentrations
cyclosporin
kidney transplantation
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
10
09
2018
revised:
16
01
2019
accepted:
20
01
2019
pubmed:
29
1
2019
medline:
14
5
2020
entrez:
29
1
2019
Statut:
ppublish
Résumé
The immunosuppressant cyclosporin is a P-glycoprotein (P-gp) substrate whose impaired function has been associated with an increased risk of cyclosporin-induced nephrotoxicity following renal transplantation. This study investigated the relationship between blood and allograft cyclosporin concentration, and the effect of P-gp expression. Fifty biopsy samples were obtained from 39 renal transplant recipients who received cyclosporin as part of maintenance immunosuppression. Blood cyclosporin concentrations (2 hours postdose) were obtained from clinical records, matching allograft cyclosporin concentrations were measured in frozen biopsy tissue by liquid chromatography-tandem mass spectrometry, and allograft P-gp expression was assessed by immunohistochemistry. Blood and allograft cyclosporin concentrations in the 1st month post-transplantation ranged from 505-2005 μg/L and 0.01-16.7 ng/mg tissue, respectively. Dose was the only significant predictor of allograft cyclosporin concentrations (adjusted R
Identifiants
pubmed: 30690767
doi: 10.1111/bcp.13880
pmc: PMC6475688
doi:
Substances chimiques
ABCB1 protein, human
0
ATP Binding Cassette Transporter, Subfamily B
0
Calcineurin Inhibitors
0
Cyclosporine
83HN0GTJ6D
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1015-1020Informations de copyright
© 2019 The British Pharmacological Society.
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