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Clinical Assessment of Drug Transporter Inhibition Using Biomarkers: Review of the Literature (2015-2024).
J Clin Pharmacol
January 2025
Drug Metabolism and Nonclinical Pharmacokinetics, Translational Medicine, Incyte, Wilmington, DE, USA.
As part of a narrative review of various publications describing the clinical use of urine- and plasma-based drug transporter biomarkers, it was determined that the utilization of coproporphyrin I, a hepatic organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 biomarker, has been reported for 28 different drug-drug interaction (DDI) perpetrator drugs. Similarly, biomarkers for liver organic cation transporter 1 (isobutyryl-l-carnitine, N = 7 inhibitors), renal organic cation transporter 2 and multidrug and toxin extrusion proteins (N-methylnicotinamide, N = 13 inhibitors), renal organic anion transporter (OAT) 1 and 3 (pyridoxic acid, N = 7 inhibitors), and breast cancer resistance protein (riboflavin, N = 3 inhibitors) have also been described. Increased use of biomarkers has also been accompanied by modeling efforts to enable DDI predictions and development of multiplexed methods to facilitate their bioanalysis.
View Article and Find Full Text PDFUltra-Sensitive Quantification of Coproporphyrin-I and -III in Human Plasma Using Ultra-Performance Liquid Chromatography Coupled to Quadrupole Time-of-Flight Mass Spectrometry.
ACS Omega
November 2024
Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
Organic anion transporting polypeptides (OATP) 1B1 and 1B3 are expressed in liver cells and are involved in drug uptake in the liver. OATP1B activity varies due to polymorphisms and is decreased by OATP1B inhibitors. Variability of OATP1B activity impacts the pharmacokinetics of OATP1B substrate drugs through drug-drug interactions.
View Article and Find Full Text PDFIncreased coproporphyrin serum levels in healthy volunteers treated with the cholesterol uptake inhibitor ezetimibe.
Clin Transl Sci
October 2024
Biopharmacy, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
Ezetimibe undergoes glucuronidation that results in the active metabolite ezetimibe phenoxy-glucuronide (ezetimibe-glucuronide). This phase-II metabolite was shown to interact with the clinically relevant hepatic transporter organic anion transporting polypeptide (OATP) 1B1. In recent years, coproporphyrin I (CPI) was established as a Tier 1 biomarker for OATP1B-mediated interactions among other endogenous substrates like CPIII.
View Article and Find Full Text PDFAltered bile acid and coproporphyrin-I disposition in patients with autosomal dominant polycystic kidney disease.
Br J Clin Pharmacol
September 2024
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.
Synergistic increase in coproporphyrin III biosynthesis by mitochondrial compartmentalization in engineered .
Synth Syst Biotechnol
December 2024
State Key Lab of Bioreactor Engineering, Newworld Institute of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China.
Coproporphyrin III (CP III), a natural porphyrin derivative, has extensive applications in the biomedical and material industries. has previously been engineered to highly accumulate the CP III precursor 5-aminolevulinic acid (ALA) through the C4 pathway. In this study, a combination of cytoplasmic metabolic engineering and mitochondrial compartmentalization was used to enhance CP III production in .
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