A tissue distribution, excretion, and metabolism study was conducted using a relatively non-toxic dioxin congener, i.e., 1,2,7,8-tetrachlorodibenzo-p-dioxin (1278-TCDD), to gain a better understanding of mammalian metabolism of dioxins. Conventional, bile duct cannulated, and germ free male rats were administered mg/kg quantities as a single oral dose. Elimination of 1278-TCDD was largely complete by 72 h. Distribution of [14C]1278-TCDD was low in all tissues examined. Metabolites were identified in urine, bile, and feces by negative ion FAB-MS and 1H-NMR, or GC/MS. The major fecal metabolite was a NIH-shifted hydroxylated TCDD. The bile contained a glucuronide conjugate of this hydroxy TCDD, and a diglucuronide conjugate of a dihydroxy-triCDD. The major metabolites in urine were glucuronide and sulfate conjugates of 4,5-dichlorocatechol.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/s0045-6535(00)00131-4 | DOI Listing |
Fluids Barriers CNS
January 2025
Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven - University of Leuven, O&N II Herestraat 49 box 820, 3000, Leuven, Belgium.
Background: Therapeutic antibodies for the treatment of neurological disease show great potential, but their applications are rather limited due to limited brain exposure. The most well-studied approach to enhance brain influx of protein therapeutics, is receptor-mediated transcytosis (RMT) by targeting nutrient receptors to shuttle protein therapeutics over the blood-brain barrier (BBB) along with their endogenous cargos. While higher brain exposure is achieved with RMT, the timeframe is short due to rather fast brain clearance.
View Article and Find Full Text PDFAnn Clin Microbiol Antimicrob
January 2025
Laboratoire des Mycobactéries, Institut des Agents Infectieux, Laboratoire de Biologie Médicale Multi-Site, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France.
Background: Mycobacterium abscessus (MABS) causes difficult-to-treat pulmonary and extra-pulmonary infections. A combination therapy comprising amikacin, cefoxitin, and a macrolide agent is recommended, but its antimicrobial activity and clinical efficacy is uncertain. Inducible resistance to macrolides (macrolides-iR) has been associated with poor clinical response in pulmonary infections, whilst for extra-pulmonary infections data are scarce.
View Article and Find Full Text PDFDrug Metab Dispos
January 2025
Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical Sciences, China Pharmaceutical University, Nanjing, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China. Electronic address:
Silybin, a milk thistle extract, is a flavonolignan compound with hepatoprotective effect. It is commonly used in dietary supplements, functional foods, and nutraceuticals. However, the metabolism of silybin has not been systematically characterized in organisms to date.
View Article and Find Full Text PDFDrug Metab Dispos
January 2025
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.
Evidence-based dose selection of drugs in pregnant women has been lacking because of challenges in studying maternal-fetal pharmacokinetics. Hence, many drugs are administered off-label during pregnancy based on data obtained from nonpregnant women. During pregnancy, drug transporters play an important role in drug disposition along with known gestational age-dependent changes in physiology and drug-metabolizing enzymes.
View Article and Find Full Text PDFDrug Metab Dispos
January 2025
Global Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy.
Tanimilast is an inhaled phosphodiesterase-4 inhibitor currently in phase III clinical development for treating chronic obstructive pulmonary disease and asthma. This trial aimed to characterize the pharmacokinetics, mass balance, and metabolite profiling of tanimilast. Eight healthy male volunteers received a single dose of nonradiolabeled tanimilast via powder inhaler (Chiesi NEXThaler [3200 μg]), followed by a concomitant intravenous infusion of a microtracer ([C]-tanimilast: 18.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!