Dexamethasone transport

Not all transporters, however, show the same preferential directions. Lee and coworkers also have discovered a pump glycoprotein in the conjunctiva with preferential flux directed toward the mucosal side of the tissue. This transporter has been shown to restrict conjunctival absorption of therapeutic agents such as cyclosporin A, verapamil, and dexamethasone. In some circumstances, transient inhibition of such xe-nobiotic transporters might be an effective means of increasing the efficacy of particular classes of therapeutic agents. 

Yamashita et al. [82] added up to 10 mM taurocholic acid, cholic acid (cmc 2.5 mM), or sodium laurel sulfate (SLS low ionic strength cmc 8.2 mM) to the donating solutions in Caco-2 assays. The two bile acids did not interfere in the transport of dexamethasone. However, SLS caused the Caco-2 cell junctions to become leakier, even at the sub-CMC 1 mM level. Also, the permeability of dexamethasone decreased at 10 mM SLS. 

Fig. 20.11. Substrate quality obtained by comparing basolateral-to-apical with apical-to-basolateral transport of substrates in polarized cell monolayers of MDR1-transfected cell lines [86] plotted versus (A) the log of the air/water partition coefficient, or (B) H-bond energy (arbitrary units, EUh cf. text). Units of the air/ water partition coefficient were [M ]. Compound (concentrations in Ref. [86] in brackets) were clozapine (50 nM) (1) cyclosporin A (2 tM) (2) daunorubicin (3) dexamethasone (2 tM) (4) digoxin (2 pM) (5) domperidone (2 pM) (6) etoposide (7) flunitrazepam (500 nM) (8) haloperidol (50 nM) (9) ivermectin (50 nM) (10) loperamide (2 pM) (11) morphine (2 pM) (12) ondansetron...

R.Z. Turncliff, P.J. Meier, and K.L. Brouwer. Effect of dexamethasone treatment on the expression and function of transport proteins in sandwich-cultured rat hepatocytes. Drug Metab Dispos. 32 834—839 (2004). 

It has been suggested that an increased production of arachidonic acid following down-regulation of annexin 1 in CF patients may explain some of the associated complications of the disease (Carlstedt-Duke et al., 1986 Strandvik et al., 1988). This is based on the observation that lymphocytes from CF patients show defective inhibition of AA production by dexamethasone. Increased AA production has been reported in CF and would influence chloride transport, mucus production and calcium homeostasis (and production of the eicosanoids). The reason why annexin 1 expression is reduced in these patients is at present unclear. 

Fleck C, Bachner B, Gockeritz S, et al. Ex vivo stimulation of renal tubular PAH transport by dexamethasone and triiodothyronine in human renal cell carcinoma. Urol Res 2000 28 383-390. 

Ueda K, Okamura N, Hirai M, et al. Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. J Biol Chem 1992 267... 

The efflux transporter P-glycoprotein (P-gp) has been proposed as a potential therapeutic target for AD [439]. Approximately 10-35 % decrease in 125I-Ap(i 0) intracellular accumulation was observed in cells treated with rifampicin, dexamethasone, caffeine, verapamil, hyperforin, p-estradiol, and pentylenetetrazole, drugs known to induce P-gp expression [439],... 

Nelson DH and Murray DK Dexamethasone Inhibition of Hydrogen Peroxide-stimulated Glucose Transport. Endocrinology 1987 120(1) 156-159. 

PXR (SXR) RXR PB, ortho-PCBs, organochlorine pesticides, dexamethasone, pregnenalone, corticosterone, bile acids (lithocholic acid) CYP3A, CYP2B, CYP7A (repression) GST, ABC transporters... 

CPT-cAMP, RO-20-1724, and 0.1 aM dexamethasone, TEER increased to 85 0 cm. This effect on TEER was neither observed without astrocytes, nor with other sources of astrocytes (see Note 2). In these conditions, the human BBB model was also sensitive to DT (determined as described earlier) and lipopolysaccharide (EPS, as described in ref. [9]). We were, however, unable to find any indication of P-glycoprotein (P-gp) expression in these cells (determined as described in ref [7]). The relatively low TEER across the BBB model and the possible absence of P-gp expression, however, limits the appUcabitity of this constellation of human endothelial cells and rat astrocytes as a BBB cell culture model for the use for drug transport and effect screening purposes. 

The dominant path of distribution and elimination in the vitreous depends on a molecule s physicochemical properties and its substrate affinity. Lipophilic compounds, such as fluorescein (250) or dexamethasone (251), and compounds subject to active transport mechanisms, tend to be eliminated via the retina (Fig. 16). On the other hand, hydrophilic substances, such as fluorescein glucuronide, and compounds with poor retinal permeability, such as fluorescein dextran, tend to exit the vitreous anteriorly through the hyaloid membrane into the posterior chamber and subsequently into the anterior chamber, where they are subject to elimination pathways for aqueous humor (250). In general, shorter vitreal half-lives are associated with elimination through the retina, with its high surface area, whereas longer half-lives are indicative of elimination through the hyaloid membrane. 

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