mp4000234_si_001.pdf (51.87 kB)
Kidney Transplantation Down-Regulates Expression of Organic Cation Transporters, Which Translocate β‑Blockers and Fluoroquinolones
journal contribution
posted on 2016-02-19, 07:34 authored by Giuliano Ciarimboli, Rita Schröter, Ute Neugebauer, Beate Vollenbröker, Gert Gabriëls, Hrvoje Brzica, Ivan Sabolić, Gesine Pietig, Hermann Pavenstädt, Eberhard Schlatter, Bayram EdemirKidney transplanted patients are
often treated with immunosuppressive,
antihypertensive, and antibiotic drugs such as cyclosporine A (CsA),
β-blockers, and fluoroquinolones, respectively. Organic cation
transporters (OCT) expressed in the basolateral membrane of proximal
tubules represent an important drug excretion route. In this work,
the renal expression of OCT after syngeneic and allogeneic kidney
transplantation in rats with or without CsA immunosuppression was
studied. Moreover, the interactions of CsA, β-blockers (pindolol/atenolol),
and fluoroquinolones (ofloxacin/norfloxacin) with rOCT1, rOCT2, hOCT1,
and hOCT2 in stably transfected HEK293-cells were studied. Kidney
transplantation was associated with reduced expression of rOCT1, while
rOCT2 showed only reduced expression after allogeneic transplantation.
All drugs interacted subtype- and species-dependently with OCT. However,
only atenolol, pindolol, and ofloxacin were transported by hOCT2,
the main OCT in human kidneys. While CsA is not an OCT substrate,
it exerts a short-term effect on OCT activity, changing their affinity
for some substrates. In conclusion, appropriate drug dosing in transplanted
patients is difficult partly because OCT are down-regulated and because
concomitant CsA treatment may influence the affinity of the transporters.
Moreover, drug–drug competition at the transporter can also
alter drug excretion rate.
History
Usage metrics
Categories
Keywords
drug excretion rateantibiotic drugsdrug dosingallogeneic transplantationOCT activityhOCT 2basolateral membraneOrganic cation transportersCsA treatmentrOCT 2CsA immunosuppressionexpressionKidney transplantationdrugs interacted subtypeHEKdrug excretion routeOCT substrateallogeneic kidney transplantationOrganic Cation Transporters
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC