Modulation of Rat Hepatic CYP1A and 2C Activity by Honokiol and Magnolol: Differential Effects on Phenacetin and Diclofenac Pharmacokinetics In Vivo Honokiol (2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol) and magnolol (4-Allyl-2-(5-allyl-2-hydroxy-phenyl)phenol) are the major active polyphenol constituents of (Magnoliaceae) bark, which has been widely used in traditional Chinese (probe substrate: phenacetin) more potently than CYP2C activity (probe substrate: diclofenac): The mean IC values of honokiol for the metabolism of phenacetin and diclofenac were 8.59 μM and 44.7 μM, while those of magnolol were 19.0 μM and 47.3 μM, respectively. Notably, the systemic exposure (AUC and C) of phenacetin, but not of diclofenac, was markedly enhanced by the concurrent administration
Increased Phenacetin Oxidation upon the L382V Substitution in Cytochrome P450 1A2 is Associated with Altered Substrate Binding Orientation Leucine382 of cytochrome P450 1A2 (CYP1A2) plays an important role in binding and -dealkylation of phenacetin, with the L382V mutation increasing substrate oxidation (Huang and Szklarz, 2010, . 38:1039⁻1045). This was attributed to altered substrate binding orientation, but no direct experimental evidence had been available. Therefore, in the current studies, we employed nuclear magnetic resonance (NMR) longitudinal (T₁) relaxation measurements to investigate phenacetin binding orientations within the active site of CYP1A2 wild type (WT) and mutants. Paramagnetic relaxation time (T) for each proton of phenacetin was calculated from the T₁ value obtained from
Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses–Induced Hepatotoxicity in Rats Both paracetamol (PA) and phenacetin (PH) are analgesic and antipyretic agents. Part of phenacetin therapeutic activity is attributed to its metabolism into paracetamol. Paracetamol causes direct hepatic oxidative
Preoperative Phenacetin Metabolism Test in the Prediction of Postoperative Liver Dysfunction of Patients with Hepatocellular Carcinoma BACKGROUND The risk of postoperative liver dysfunction (PLD) in patients with injured livers, such as in hepatocellular carcinoma (HCC), is still not negligible. Phenacetin metabolism test can reflect hepatic functional reserve in patients with chronic hepatic damage. The aim of this study was to assess the ability of phenacetin metabolism test to predict PLD in patients with HCC receiving partial hepatectomy. MATERIAL AND METHODS Forty-nine patients with HCC undergoing partial hepatectomy between 2014 and 2016 were included at Huashan Hospital, Fudan University. The phenacetin metabolism test was used to assess the hepatic functional reserve. The ratio
such as phenacetin (available only in Japan), cyclophosphamide or ifosfamide chemotherapy, and aristolochic acid in some herbal weight loss preparations).[8] Asymptomatic NVH is more likely to be associated with urinary tract malignancy in men.[11][3] Obesity and hypertension are risk factors for renal cell carcinoma.[12]If malignancy is suspected, based on a high-risk or intermediate-risk profile
on Substance Use and Addiction • Centre canadien sur les dépendances et l’usage de substances Page 10 decreased, with 77% of expected cocaine substances containing only cocaine between January and July 2022, compared with 45% in 2020. Phenacetin‖ and levamisole¶ are noteworthy contaminants found in cocaine and crack cocaine most often. Local Responses • Harm reduction programs provide safer drug use and freebase) was reported by 59% of the participants. It was detected in the urine of 91% of those who reported having used it. Methamphetamine and crystal meth use were reported by 15% and 14% of participants, respectively. Crack and crystal meth were reported more frequently in the greater Montreal region. (Also see Figures 1 and 4 .) ‖ A pain-relieving, fever-reducing medication, phenacetin
, and six of the nine also contained metonitazene and etodesnitazene. Most samples were expected to be other opioids or “down.” BCCSU-partnered sites have also identified isotonitazene, etodesnitazene (in some cases alongside clonazolam, phenacetin, erythritol, caffeine or fentanyl), metonitazene and protonitazene. Protonitazene was linked to nine deaths in a 2021 report,1 three of which were in B.C
Sulfate" or mavatrep or Medetomidine or Methotrimeprazine or Milnacipran or Mitoxantrone or Nefopam or neurotropin or "Nitrous Oxide" or nuvanil or olodanrigan or olorinab or olvanil or "omega conotoxin" or panidex or "pf 3557156" or "pf 4136309" or "pf 4480682" or "pf 592379" or "pf 738502" or Phenacetin or Pizotyline or pravadoline or Pregabalin or Quinine or ralfinamide or retigabine or ruzadolane
and diphenhydramine. - Excluding cutting agents, 11% contained additional psychoactive substances. • Nearly a third (29%) of cocaine-containing samples also contained additional substances, much of this accounted for by cutting agents such as phenacetin, local anesthetics and levamisole. - Excluding cutting agents, 5% contained additional psychoactive substances. Table 1a. Non-opioid substances in opioid-containing agents3 Caffeine: 13,818 (59%) Dimethylsulfone: 2,963 (13%) Non-opioid analgesics:4 1,903 (8%); of these, 340 (18%) phenacetin Table 1b. Specific opioids of interest in opioid-containing samples submitted to DAS (April 2018 – August 2019; n = 23,338) Opioid of interest Appears in number (%) of samples Heroin 5,136 (22%) Fentanyl or fentanyl analogues 14,424 (62%); of these, 1,999 (14%) carfentanil Non
was performed in multiple reaction monitoring (MRM) mode with the transitions of m/z 410.2→126.1 for GL-V9, m/z 586.3→410.0 for 5-O-glucuronide GL-V9 and m/z 180.0→110.3 for phenacetin (internal standard), respectively. The calibration curves for GL-V9 and 5-O-glucuronide GL-V9 showed excellent linearity over the concentration range of 0.5-500 ng/mL with correlation coefficient greater than 0.99. The intra
such as phenacetin (available only in Japan), cyclophosphamide or ifosfamide chemotherapy, and aristolochic acid in some herbal weight loss preparations).[8]Cohen RA, Brown RS. Microscopic hematuria. N Engl J Med. 2003;348:2330-2338.http://www.ncbi.nlm.nih.gov/pubmed/12788998?tool=bestpractice.com Asymptomatic NVH is more likely to be associated with urinary tract malignancy in men.[11]Committee on Gynecologic
. To explore the DDI between BX and CW, in the pharmacokinetics study, 10 compounds were determined in rat plasma after administering CW and BX-CW herbal pair extracts. In the cocktail assay, the pharmacokinetic parameters of five probe substrates were utilized to assess the influence of BX on cytochrome P450 (CYP) isoenzyme (dapsone for CYP3A4, phenacetin for CYP1A2, dextromethorphan for CYP2D6, tolbutamide
of induced hepatotoxicity and CYP1A2 mRNA and protein expression in vivo and in vitro, as well as the effect on CYP1A2 enzyme activity evaluated by phenacetin metabolism. In addition, the potential mechanism of the regulation of CYP1A2 expression mediated by AhR was explored through nucleocytoplasmic shuttling, immunofluorescence, cellular thermal shift assay and molecular docking, etc. RESULTS: Psoralen
Preferred Binding Orientations of Phenacetin in CYP1A1 and CYP1A2 Are Associated with Isoform-Selective Metabolism Human cytochromes P450 1A1 and 1A2 play important roles in drug metabolism and chemical carcinogenesis. Although these two enzymes share high sequence identity, they display different substrate specificities and inhibitor susceptibilities. In the present studies, we investigated the structural basis for these differences with phenacetin as a probe using a number of complementary approaches, such as enzyme kinetics, stoichiometric assays, NMR, and molecular modeling. Kinetic and stoichiometric analyses revealed that substrate specificity (k(cat)/K(m)) of CYP1A2 was approximately 18-fold greater than that of CYP1A1, as expected. Moreover, despite higher H₂O₂ production, the coupling