The effect of propranolol on paracetamol metabolism in man.

Abstract

Ten healthy volunteers were treated for 4 days with 160 mg propranolol HCl and placebo in random order. At the end of each treatment salivary antipyrine kinetics and the plasma kinetics and urinary excretion of paracetamol and its major metabolites were measured following a 1500 mg oral dose. Propranolol prolonged the half-life of antipyrine by 11 ± 5% (mean ± s.e. mean) and lowered its clearance by 14 ± 3% (P < 0.05). Propranolol increased the half-life of paracetamol by 25 ± 12% (P < 0.05) and lowered its clearance by 14 ± 3% (P < 0.05). Propranolol decreased the partial clearance of paracetamol to its cysteine and mercapturate derivatives by 16 ± 3% (P < 0.05) and 32 ± 7% (P < 0.05), respectively. The partial clearance to the glucuronide conjugate was decreased by 27 ± 6% (P < 0.05), whereas that to sulphate was not changed significantly. Propranolol inhibits paracetamol metabolism predominantly through inhibition of the oxidation and glucuronidation pathways.Keywords drug metabolism drug interaction propranolol paracetamol antipyrine

Glucosamine Enhances Paracetamol Bioavailability by Reducing Its Metabolism

“…The latter reduction was even more than propranolol, a known inhibitor to paracetamol metabolism. It has been shown in a human study that propranolol increased the BA of 1500 mg dose of paracetamol by reducing its oxidation and glucuronidation pathways . Furthermore, our docking results indicate that GlcN, to some extent, is capable of competing with the paracetamol molecules on the catalytic pocket of the human CYP2E1 protein.…”

Rapid identification of potential nonsteroidal anti‐inflammatory drug overdose–induced liver toxicity and prediction of follow‐up exposure: Integrating bioanalytical and population pharmacokinetic assay

“…One hundred twenty‐one APAP concentrations (Achterbergh et al, 2019; Baraka et al, 1990; Garcia Aguirre et al, 2019; Grattan et al, 2000; Raffa et al, 2018; Seideman, 1991; Singla et al, 2012; Volak et al, 2013; Yin et al, 2001), 145 FLB concentrations (Greenblatt et al, 2006; Hanley et al, 2013; Liu et al, 2009; Ozbay et al, 2009; Qayyum et al, 2011; Szpunar et al, 1987; Taburet et al, 1995), 124 ASP concentrations (Angiolillo et al, 2020; Benedek et al, 1995; Cryer et al, 1999; Hobl et al, 2015; Husted et al, 1983; Itthipanichpong et al, 1992; Koch et al, 1978; Misawa et al, 1985; Muir et al, 1997; Nakayasu et al, 2003), and 306 IBP concentrations (Al‐Meshal et al, 1994; De Brabander et al, 2004; Dewland et al, 2009; Gillespie et al, 1982; Hammami et al, 2017; Hattrem et al, 2018; Idkaidek & Arafat, 2011; Kapil et al, 2004; Kimura et al, 1992; Koenigsknecht et al, 2017; Laneury et al, 1998; Lapatto‐Reiniluoto et al, 1999; Neuvonen, 1991; Shin et al, 2017; Sugár et al, 2019) were extracted from 11 groups of APAP data, 11 groups of FLB data, 14 groups of ASP data, and 22 groups of IBP data. Demographics and study details are summarized in Table S1, and the line charts of plasma concentration–time after doses are shown in Figure S1.…”

Inhibition of human UDP‐glucuronosyltransferase enzyme by Dabrafenib: Implications for drug–drug interactions

“…It is estimated that UGTs accounted for about 35% of all drugs metabolized by phase II drug‐metabolizing enzymes (Guillemette, 2003), and some chemical carcinogens, dietary substances and environmental pollutants (Ritter, 2000). There is clinical evidence that the glucuronidation of zidovudine, acetaminophen and other drugs can be affected by specific interacting drugs (Baraka et al, 1990; Ethell et al, 2003). UGT inhibition can also lead to hepatotoxicity and clinically significant DDIs (Meech et al, 2019).…”