The Brain, Amphotericin B, and P-Glycoprotein

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The brain, amphotericin B, and P-glycoprotein.

We read with interest the paper by Wu et al. (1) purporting to show that blockade of P-glycoprotein with verapamil or itraconazole increased brain concentrations of amphotericin B (AMB). Because virtually all P-glycoprotein blockers also block other transporters, we chose to compare P-glycoprotein knockout (KO) mice (Mdr1a/1b) with isogenic FVB wild-type mice. After administration of intravenou...

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Reply to "the brain, amphotericin B, and p-glycoprotein".

We thank David A. Stevens et al. (1) for the letter suggesting different results regarding the effect of P-glycoprotein on the brain concentration of amphotericin B (AMB) by P-glycoprotein knockout mice. In contrast to our finding that blockage of P-glycoprotein with inhibitors enhances the brain uptake of AMB (2), they found that brain AMB concentrations were significantly lower in Mdr1a/1b / ...

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In vitro and in vivo evidence for amphotericin B as a P-glycoprotein substrate on the blood-brain barrier.

Amphotericin B (AMB) has been a mainstay therapy for fungal infections of the central nervous system, but its use has been limited by its poor penetration into the brain, the mechanism of which remains unclear. In this study, we aimed to investigate the role of P-glycoprotein (P-gp) in AMB crossing the blood-brain barrier (BBB). The uptake of AMB by primary brain capillary endothelial cells in ...

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Plasma protein binding of amphotericin B and pharmacokinetics of bound versus unbound amphotericin B after administration of intravenous liposomal amphotericin B (AmBisome) and amphotericin B deoxycholate.

Unilamellar liposomal amphotericin B (AmBisome) (liposomal AMB) reduces the toxicity of this antifungal drug. The unique composition of liposomal AMB stabilizes the liposomes, producing higher sustained drug levels in plasma and reducing renal and hepatic excretion. When liposomes release their drug payload, unbound, protein-bound, and liposomal drug pools may exist simultaneously in the body. ...

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The Role of P-glycoprotein in the Blood-Brain Barrier

The blood-brain barrier is composed of specialized endothelial cells that prevent various substances from entering the brain. P-glycoprotein is an important component of this barrier and is present in high concentration on the apical surface of these endothelial cells. It is an ATP-dependent transport protein thought to be involved in extruding a variety of structurally unrelated compounds and ...

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ژورنال

عنوان ژورنال: Antimicrobial Agents and Chemotherapy

سال: 2015

ISSN: 0066-4804,1098-6596

DOI: 10.1128/aac.04768-14