Kinetics in serum and urinary excretion of ethyl sulfate and ethyl glucuronide after medium dose ethanol intake

Abstract

The direct ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS), are of increasing importance for clinical and forensic applications, but there are only few studies on the kinetics of EtG in serum and none on EtS. In this study, 13 volunteers (social drinkers) drank ethanol in the form of white wine to reach a blood alcohol concentration of 0.51 +/- 0.17 g/kg, and blood and urine samples were analyzed for EtG and EtS simultaneously by chromatography-tandem mass spectrometry (LC-MS/MS). Mean peak serum EtG and EtS concentrations were 2.9 +/- 1.3 and 2.8 +/- 1.6 micromol/l, respectively, and were reached between 4.0 +/- 0.9 h after the start of drinking (3.0 +/- 0.5 h for EtS). The mean time differences between reaching maximum blood ethanol levels and serum metabolite levels were 2.3 +/- 0.9 h for EtG and 1.2 +/- 0.5 h for EtS. In the last blood samples collected (10-11 h after the start of drinking), 11 (of 13) volunteers were still positive for EtG in serum, whereas only 2 were positive for EtS. In the serum of one female person, no EtS was detectable at any time; however, it was excreted in the urine in (low) concentrations. Ethanol was detectable in the serum for up to 8.6 h after the start of drinking, whereas EtG and EtS were detectable up to more than 5.8 h (EtG) and 4.0 h (EtS), respectively. Mean peak urinary concentrations were 401 +/- 232 micromol/l for EtG and 266 +/- 153 micromol/l for EtS, and mean peak levels were reached 6.2 +/- 0.9 h (EtG) and 5.3 +/- 1.2 h (EtS) after the start of drinking. Maximum concentrations of EtG and EtS in serum showed a wide interindividual variation and could not be correlated to the maximum blood ethanol concentrations. Correlations (p < 0.001, Kendall's Tau b) were found when comparing pairs of parameters, but mostly involved areas under the curve (AUC) of metabolites or of ethanol; one correlation linked the peak concentrations of EtG and EtS in urine.

Ethanol Sulfation by the Human Cytosolic Sulfotransferases: A Systematic Analysis

“…Previous studies have demonstrated the presence of ethyl sulfate in the liver and kidney as well as in urine and blood of drinkers. 5,16,38) To obtain evidence for the presence of ethanol-sulfating activity in human tissues, enzymatic assays were performed using cytosol or S9 fraction prepared from human lung, liver, small intestine, or kidney. Results showed clearly the presence of sulfating activities toward ethanol in samples prepared from lung, liver, and small intestine.…”

“…3,4) Upon ethanol ingestion, ethyl sulfate and ethyl glucuronide are excreted for a considerably longer period of time than ethanol, hence allowing urine testing of these minor ethanol metabolites as a sensitive method to screen for alcohol ingestion. 3,[5][6][7] More recently, ethyl sulfate and ethyl glucuronide have also been implicated as biomarkers for in utero exposure to ethanol. [8][9][10] While the physiological relevance of ethanol sulfation remains unknown, the capacity of metabolizing ethanol to acetate had been shown to be much lower in fetuses than in adults due to the low level of the activity of alcohol dehydrogenase.…”

Involvement of UDP-Glucuronosyltransferases UGT1A9 and UGT2B7 in Ethanol Glucuronidation, and Interactions with Common Drugs of Abuse

“…However, considering the numerous factors that could affect glucuronidation (e.g., genetic polymorphisms, inhibition or induction by xenobiotics, and age), the relevance of these cutoffs in clinical and forensic practices can be questioned in certain circumstances (Kiang et al, 2005). Some reports have indeed documented a high interindividual variability in EtG production (Halter et al, 2008;Paul et al, 2008). Halter et al (2007) showed that the administration of a conventional dose of ethanol to 13 individuals resulted in highly variable (8-fold) maximum concentrations of serum EtG, and that EtG concentrations did not correlate with blood ethanol concentrations (Halter et al, 2008).…”

“…Some reports have indeed documented a high interindividual variability in EtG production (Halter et al, 2008;Paul et al, 2008). Halter et al (2007) showed that the administration of a conventional dose of ethanol to 13 individuals resulted in highly variable (8-fold) maximum concentrations of serum EtG, and that EtG concentrations did not correlate with blood ethanol concentrations (Halter et al, 2008). This marked interindividual variability in EtG levels could be attributed to variable activities of UGTs involved in ethanol metabolism.…”

Ethyl glucuronide

“…7,8 There appear to be wide interindividual variations in the maximum plasma EtG and EtS concentrations and there is no correlation between the metabolites and blood ethanol concentration. 7 Studies have found that metabolite elimination occurs exponentially with a median half-life of between 2 and 4 h. 8 -10 EtG can usually be detected in the urine for between 72 and 90 h.…”