Metabolism of AM404 From Acetaminophen at Human Therapeutic Dosages in the Rat Brain.

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Muramatsu S, Shiraishi S, Miyano K, Sudo Y, Toda A, Mogi M, Hara M, Yokoyama A, Kawasaki Y, Taniguchi M, Uezono Y

Metabolism of AM404 From Acetaminophen at Human Therapeutic Dosages in the Rat Brain.

Anesth Pain Med. 2016 Jan 17;6(1):e32873. doi: 10.5812/aapm.32873. eCollection 2016 Feb.

PubMed ID

27110534 [ View in PubMed

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Abstract

BACKGROUND: Acetaminophen, an analgesic and antipyretic drug, has been used clinically for more than a century. Previous studies showed that acetaminophen undergoes metabolic transformations to form an analgesic compound, N-(4-hydroxyphenyl) arachidonamide (AM404), in the rodent brain. However, these studies were performed with higher concentrations of acetaminophen than are used in humans. OBJECTIVES: The aim of the present study was to examine the metabolism of AM404 from acetaminophen in the rat brain at a concentration of 20 mg/kg, which is used in therapeutic practice in humans, and to compare the pharmacokinetics between them. MATERIALS AND METHODS: We used rat brains to investigate the metabolism of AM404 from acetaminophen at concentrations (20 mg/kg) used in humans. In addition, we determined the mean pharmacokinetic parameters for acetaminophen and its metabolites, including AM404. RESULTS: The maximum plasma concentrations of acetaminophen and AM404 in the rat brain were 15.8 microg/g and 150 pg/g, respectively, with corresponding AUC0-2h values of 8.96 mug hour/g and 117 pg hour/g. The tmax for both acetaminophen and AM404 was 0.25 hour. CONCLUSIONS: These data suggest that AM404's concentration-time profile in the brain is similar to those of acetaminophen and its other metabolites. Measurement of blood acetaminophen concentration seems to reflect the concentration of the prospective bioactive substance, AM404.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Acetaminophen	Fatty-acid amide hydrolase 1	Protein	Humans	Unknown	Substrate	Details