The effects of OATP1B1, OAT3, and MRP2 on the pharmacokinetics of eluxadoline, an oral, locally active, opioid receptor agonist/antagonist being developed for treatment of IBS-d were assessed in vivo. Coadministration of a single 200 mg dose of eluxadoline with cyclosporine, and probenecid increased eluxadoline systemic exposure [AUC(0-inf) ] by 4.4- and 1.4-fold, respectively, whereas peak exp...

Liver sinusoidal endothelial cells (LSECs) are specialized scavenger cells that mediate high-capacity clearance of soluble waste macromolecules and colloid material, including blood-borne adenovirus. To explore if LSECs function as a sink for other viruses in blood, we studied the fate of virus-like particles (VLPs) of two ubiquitous human DNA viruses, BK and JC polyomavirus, in mice. Like comp...

somatostatin-like immunoreactivity (SLI) was assessed simultaneously in an in vivo dog model. The hepatic extraction of this peptide was 29.4+±2.3% and was similar for endogenous and infused exogenous SLI. The renal extraction was 62.3±+5%. The renal clearance of SLI was significantly greater than that of inulin indicating that the peptide is handled by peritubular uptake from postglomerular bl...

A direct consequence of glomerular protein leakage is an increased exposure of proximal tubular cells to proteins. The aim of the present study was to examine whether chronic proteinuria affects the tubular handling of proteins and whether anti-proteinuric therapy by angiotensin-converting-enzyme (ACE) inhibition restores this tubular function. Renal uptake and catabolic rate of the low-molecul...

Amoxicillin and cefaclor are two of the widely used beta-lactam antibiotics in the treatment of urinary tract infections. Both drugs are eliminated mainly by the kidney and rely on renal excretion to exert their antibacterial activities in the urinary tract. Previous studies have suggested the involvement of organic anion and oligopeptide transporters in membrane transport of beta-lactams. The ...

objective(s): in line with previous research on the development of conjugated bisphosphonate ligands as new bone-avid agents, in this study, dota conjugated alendronate (dota-aln) was synthesized and evaluated after labeling with gallium-68 (68ga).methods: dota-aln was synthesized and characterized, followed by 68ga-dota-aln preparation, using dota-aln and 68gacl3 (ph: 4-5) at 92-95°c for 10 mi...

Organic anion transporter 3 (Oat3) is a major renal Oats expressed in the basolateral membrane of renal proximal tubule cells. We have recently reported decreases in renal Oat3 function and expression in diabetic rats and these changes were recovered after insulin treatment for four weeks. However, the mechanisms by which insulin restored these changes have not been elucidated. In this study, w...

d-Glutamate (Glu) was previously shown to block l-Glu uptake and accelerate glutaminase flux in cultured kidney cells [Welbourne, T. C., and D. Chevalier. Am. J. Physiol. 272 ( Endocrinol. Metab. 35): E367-E370, 1997]. To test whether d-Glu would be taken up by the intact functioning kidney and effect the same response in vivo, male Sprague-Dawley rats were infused withd-Glu (2.6 μmol/min), and...

The driving forces mediating tetraethylammonium (TEA) transport were systematically assessed in Xenopus oocytes and MDCK cells expressing organic cation transporter (OCT) 2 cloned from rat kidney (rOCT2). In rOCT2 cRNA-injected oocytes, uptake of [14C]TEA was saturable, with an estimated Michaelis constant ( K m) of 393 μM, and was specifically inhibited by organic cations. Furthermore, TEA upt...

BACKGROUND Brincidofovir (BCV) is an orally bioavailable lipid conjugate of cidofovir (CDV) with increased in vitro potency relative to CDV against all 5 families of double-stranded DNA viruses that cause human disease. After intravenous (IV) administration of CDV, the organic anion transporter 1 (OAT1) transports CDV from the blood into the renal proximal tubule epithelial cells with resulting...