A kinetic study of the main guaco metabolites using syrup formulation and the identification of an alternative route of coumarin metabolism in humans

PloS One
João Cleverson GasparettoRoberto Pontarolo

Abstract

For decades guaco species have been empirically used for the treatment of respiratory diseases. However, studies have shown that the toxic and therapeutic effects of the main guaco metabolites are dose-dependent, and none clinical study was done to evaluate the behavior of these substances in humans. In this work, a pilot study measuring the kinetic profile of the main guaco metabolites was performed leading to the knowledge of an alternative route of coumarin metabolism in humans. Initial screenings demonstrated that the administration of 60 mL of guaco syrup (single dose) did not provide sufficient levels of coumarin (COU), 7-hydroxycoumarin (7-HCOU), o-coumaric acid (OCA) and kaurenoic acid (KAU). The pharmacokinetic parameters were calculated by orally administering 60 mL of guaco syrup spiked with 1500 mg of COU. The kinetic study demonstrated that the plasmatic levels of 7-HCOU (considered the main metabolite of COU) were 10 times lower than the levels of COU, and the kinetic profile of 7-HCOU suggests sequential metabolism in the liver with low access of 7-HCOU to the systemic circulation. The study also demonstrated that OCA is one of the main bioavailable metabolites of COU. Therefore, the hydrolysis of the lactone rin...Continue Reading

References

Dec 28, 1977·European Journal of Clinical Pharmacology·W A RitschelK W Grummich
Aug 1, 1991·British Journal of Clinical Pharmacology·Y H ParkR K Brazzell
Jan 1, 1987·Cancer Immunology, Immunotherapy : CII·L PedersenE Langvad
Feb 15, 1969·Nature·W H ShillingR C Longland
Aug 7, 1982·Lancet·R D ThornesM V Sheehan
Jan 1, 1981·Pharmacology & Therapeutics·J B Houston
Dec 1, 1982·British Journal of Clinical Pharmacology·V RoveiM Strolin Benedetti
Jan 1, 1994·Journal of Cancer Research and Clinical Oncology·R D ThornesE Gaffney
Oct 1, 1993·Regulatory Toxicology and Pharmacology : RTP·J H McGeeR D Sofia
Jul 27, 1999·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·B G Lake
Aug 4, 1999·Journal of Ethnopharmacology·I M FierroC Barja-Fidalgo
Mar 27, 2001·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·R A FordA M Api
Feb 23, 2002·The Journal of Pharmacy and Pharmacology·R Soares de MouraL C R M Carvalho
Aug 8, 2002·Toxicon : Official Journal of the International Society on Toxinology·L V Costa-LotufoV S N Rao
Sep 19, 2002·Phytotherapy Research : PTR·E S SuyenagaA T Henriques
Jun 5, 2004·European Journal of Pharmacology·Carlos R TirapelliAna M de Oliveira
Dec 17, 2004·Journal of Veterinary Pharmacology and Therapeutics·P L Toutain, A Bousquet-Mélou
Apr 28, 2005·The Journal of Experimental Biology·Craig R White, Roger S Seymour
Aug 9, 2005·Journal of Ethnopharmacology·D RamanitrahasimbolaM Nicoletti
Sep 27, 2005·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·B C CavalcantiC Pessoa
Mar 18, 2009·European Journal of Pharmacology·Juliana F VasconcelosMilena B P Soares
Oct 7, 2009·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Scott S AuerbachRajendra S Chhabra
Jul 20, 2010·The Journal of Pharmacy and Pharmacology·Marcelo H Napimoga, Regiane Yatsuda
Jan 8, 2011·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Ran Joo ChoiYeong Shik Kim
Sep 29, 2011·Annual Review of Pharmacology and Toxicology·M K DeGorterR B Kim
Mar 15, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hanneke G M WittgenFrans G M Russel

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Citations

Nov 23, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Letícia Paula LeonartRoberto Pontarolo
Jul 3, 2020·International Journal of Molecular Sciences·Francesca AnnunziataAndrea Pinto

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BETA
blood collection
MDS

Software Mentioned

MS Workstation
WinNonlin Professional
Analyst

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