Systemic availability and pharmacokinetics of thymol in humans

J Clin Pharmacol. 2002 Jul;42(7):731-7. doi: 10.1177/009127002401102678.

Abstract

Essential oil compounds such as found in thyme extract are established for the therapy of chronic and acute bronchitis. Various pharmacodynamic activities for thyme extract and the essential thyme oil, respectively, have been demonstrated in vitro, but availability of these compounds in the respective target organs has not been proven. Thus, investigation of absorption, distribution, metabolism, and excretion are necessary to provide the link between in vitro effects and in vivo studies. To determine the systemic availability and the pharmacokinetics of thymol after oral application to humans, a clinical trial was carried out in 12 healthy volunteers. Each subject received a single dose of a Bronchipret TP tablet, which is equivalent to 1.08 mg thymol. No thymol could be detected in plasma or urine. However, the metabolites thymol sulfate and thymol glucuronide were found in urine and identified by LC-MS/MS. Plasma and urine samples were analyzed after enzymatic hydrolysis of the metabolites by headspace solid-phase microextraction prior to GC analysis and flame ionization detection. Thymol sulfate, but not thymol glucuronide, was detectable in plasma. Peak plasma concentrations were 93.1+/-24.5 ng ml(-1) and were reached after 2.0+/-0.8 hours. The mean terminal elimination half-life was 10.2 hours. Thymol sulfate was detectable up to 41 hours after administration. Urinary excretion could be followed over 24 hours. The amount of both thymol sulfate and glucuronide excreted in 24-hour urine was 16.2%+/-4.5% of the dose.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-Infective Agents / pharmacokinetics*
  • Anti-Infective Agents / urine
  • Area Under Curve
  • Biological Availability
  • Chromatography, High Pressure Liquid
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Male
  • Plant Extracts / blood
  • Plant Extracts / pharmacology
  • Plant Extracts / urine
  • Primula / chemistry
  • Thymol / blood
  • Thymol / pharmacokinetics*
  • Thymol / urine

Substances

  • Anti-Infective Agents
  • Plant Extracts
  • Thymol