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Altered bile acid and coproporphyrin-I disposition in patients with autosomal dominant polycystic kidney disease.
Br J Clin Pharmacol
February 2025
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Article Synopsis
- * A study involving blood and urine samples from both ADPKD patients and healthy volunteers revealed significant increases in toxic bile acids among the ADPKD group.
- * The results suggest that elevated bile acids and specific compounds may heighten the risk of drug-induced liver injury and drug interactions in ADPKD patients due to impaired liver transport mechanisms.
Plasma and urinary CP I and CP III concentrations in chimeric mice with human hepatocytes after rifampicin administration.
Pharmacol Res Perspect
October 2024
Pharmaceutical Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa, Japan.
The interest in transporter-mediated drug interactions has been increasing in the field of drug development. In this study, we measured the plasma and urinary concentrations of coproporphyrin (CP) I and CP III as endogenous substrates for organic anion-transporting polypeptide (OATP) using chimeric mice with human hepatocytes (PXB mice) and examined the influence of an OATP inhibitor, rifampicin (RIF). CP I and CP III were actively taken up intracellularly, and RIF inhibited the uptake in a concentration-dependent manner for both CP I and CP III in human hepatocytes (PXB-cells).
View Article and Find Full Text PDFPorphyrinuria in Autism Spectrum Disorder: A Review.
Curr Med Chem
October 2024
Department of Physiology, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia.
Numerous studies demonstrated that the number of children with autism spectrum disorder (ASD) has increased remarkably in the past decade. A portion of ASD etiology, however, is attributed to environmental issues and genetic disorders. We highlighted a scoping review to principally evaluate the current information on mercury exposure in ASD children and to reveal knowledge gaps.
View Article and Find Full Text PDFUrinary coproporphyrins as a diagnostic biomarker of Dubin-Johnson syndrome in neonates: A diagnostic pathway is proposed.
Saudi J Gastroenterol
June 2023
Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.
Background: Dubin-Johnson syndrome (DJS) presents during the neonatal period with a phenotype that overlaps with a broad list of causes of neonatal cholestasis (NC), which makes the identification of DJS challenging for clinicians. We conducted a case-controlled study to investigate the utility of urinary coproporphyrins (UCP) I% as a potential diagnostic biomarker.
Methods: We reviewed our database of 533 cases of NC and identified 28 neonates with disease-causing variants in ATP-binding cassette-subfamily C member 2 (ABCC2) gene "Cases" (Study period 2008-2019).
Characterization of Elimination Pathways and the Feasibility of Endogenous Metabolites as Biomarkers of Organic Anion Transporter 1/3 Inhibition in Cynomolgus Monkeys.
Drug Metab Dispos
July 2023
Drug Metabolism, Gilead Sciences Inc., Foster City, California
Organic anion transporters 1 and 3 (OAT1/3) occupy a key role in mediating renal elimination. Kynurenic acid (KYNA) was previously discovered as an effective endogenous biomarker to assess drug-drug interaction (DDI) for OAT inhibitors. Here, further in vitro and in vivo investigation was performed to characterize the elimination routes and feasibility of KYNA, along with other reported endogenous metabolites, as biomarkers of Oat1/3 inhibition in bile duct-cannulated (BDC) cynomolgus monkeys.
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