Concise report
Effects of cyclosporin at various concentrations on dexamethasone
intracellular uptake in multidrug resistant cells
J F Mailleferta, O Duchampb, E Solaryc, P Genneb, C Taverniera
a Department of
Rheumatology, Dijon University Hospital, France, b Oncodesign, Dijon, France, c Unité INSERM
517, Faculty of Medicine and Pharmacy, Dijon, France
Correspondence to: Dr Maillefert, Department of Rheumatology, Hôpital Général, 3 rue du Fb Raines, 21000 Dijon, France
Accepted for publication 2 November 1999
BACKGROUND
The
multidrug resistance phenomenon results from the expression of
P-glycoprotein (P-gp), a drug-efflux pump. Corticosteroids are
substrates for P-gp, whose function can be inhibited by cyclosporin. This study evaluates the ability of cyclosporin to modulate
dexamethasone uptake in multidrug resistant cells.
METHODSThe K 562 cell
line, which does not express P-gp and a P-gp expressing clone,
K562/ADM, were used. Cells were incubated with H3-dexamethasone in the
absence or presence of cyclosporin at various concentrations. Then,
cells were washed, lysed, and radioactivity was measured.
RESULTSThe uptake of
dexamethasone alone was higher in sensitive than in resistant cells.
Addition of cyclosporin induced a dose dependent increase of
dexamethasone uptake in resistant cells, whereas the drug did not
influence dexamethasone uptake in parental cells.
CONCLUSIONCyclosporin,
at therapeutic concentrations induces a moderate, but significant
increase in dexamethasone accumulation in multidrug resistant cells.
Thus, cyclosporin might increase the intestinal absorption of
corticosteroids or their accumulation in mononuclear cells, or both,
thereby increasing their therapeutic efficacy.
© 2000 by Annals of the Rheumatic Diseases
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