Phase II pharmaceutical metabolites acetaminophen glucuronide and acetaminophen sulfate in wastewater

Environmental context. Excretion of pharmaceuticals and their metabolites by humans and animals, flushing unused pharmaceuticals and inadequate water treatment result in the occurrence of these chemicals as pollutants in wastewater, surface water and drinking water. In this research, the pharmaceutical agent acetaminophen (paracetamol, Tylenol) and its glucuronide and sulfate metabolites were examined as a model system for monitoring wastewater influent and effluent. The true risk to ecosystems and humans from the occurrence of pharmaceuticals in our water supply can only be estimated if accurate concentrations of parent pharmaceutical chemicals as well as their metabolites are measured. Abstract. An analytical method was developed to separately determine acetaminophen and its Phase II metabolites, acetaminophen glucuronide and acetaminophen sulfate, from wastewater in a single extract. The method developed will serve as a model for screening for the presence of other non-steroidal pharmaceutical compounds and their Phase II metabolites in wastewater. Acetaminophen glucuronide was not present in the wastewater influent tested to verify the analytical protocol, whereas concentrations of acetaminophen and acetaminophen sulfate in the influent were reproducible over time. A Phase I metabolite, p-aminophenol, was also determined to occur in the wastewater influent. Concentrations of the analytes-of-interest, detected in effluent samples collected after secondary treatment, but before UV treatment, were highly variable and were undetectable after UV treatment before release to surface water.

Effect of enteral vs. parenteral glucose delivery on initial splanchnic glucose uptake in nondiabetic humans

To determine if enteral delivery of glucose influences splanchnic glucose metabolism, 10 subjects were studied when glucose was either infused into the duodenum at a rate of 22 μmol · kg−1 · min−1 and supplemental glucose given intravenously or when all glucose was infused intravenously while saline was infused intraduodenally. Hormone secretion was inhibited with somatostatin, and glucose (∼8.5 mmol/l) and insulin (∼450 pmol/l) were maintained at constant but elevated levels. Intravenously infused [6,6-2H2]glucose was used to trace the systemic appearance of intraduodenally infused [3-3H]glucose, whereas UDP-glucose flux (an index of hepatic glycogen synthesis) was measured using the acetaminophen glucuronide method. Despite differences in the route of glucose delivery, glucose production (3.5 ± 1.0 vs. 3.3 ± 1.0 μmol · kg−1 · min−1) and glucose disappearance (78.9 ± 5.7 vs. 85.0 ± 7.2 μmol · kg−1 · min−1) were comparable on intraduodenal and intravenous study days. Initial splanchnic glucose extraction (17.5 ± 4.4 vs. 14.5 ± 2.9%) and hepatic UDP-glucose flux (9.0 ± 2.0 vs. 10.3 ± 1.5 μmol · kg−1 · min−1) also did not differ on the intraduodenal and intravenous study days. These data argue against the existence of an “enteric” factor that directly (i.e., independently of circulating hormone concentrations) enhances splanchnic glucose uptake or hepatic glycogen synthesis in nondiabetic humans.