At a glance
ClinicalIndex Comparison RecordStandardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
Allosteric Regulation of Cytosolic Sulfotransferases in Humans
In Brief
A Early Phase 1 clinical trial evaluating SULT Allosteric Inhibition for Metabolic Side Effects of Drugs. Completed, enrolled 1 participant across 1 site.
Detailed Summary
The study test whether the NSAID allosteric site of human sulfotransferase 1A1 (SULT1A1) is operative in humans. The study will test the effects of mefenamic acid (MEF) on the sulfonation of acetaminophen (APAP, a SULT1A1 specific substrate) and dehydroepiandrosterone (DHEA, a SULT2A1 substrate). If the allosteric site is active in vivo, MEF is predicted to result in a decrease in sulfonation of APAP (MEF inhibits SULT with high affinity (Ki = 23 nM), and to have no effect on sulfonation of the DHEA (MEF has little or no effect on SULT2A1 activity).
Study Details
Timeline
Interventions
A single, therapeutic dose of acetaminophen (APAP, 1.0 g)) or dehydroepiandrosterone (DHEA, 75 mg) is taken orally (with 375 ml of water) either alone or simultaneously with a single, oral, therapeutic dose of mefenamic acid (MEF, 0.75 g). In total, 5 experiments will be performed. Each experiment is performed in duplicate. Compounds are taken prior to eating breakfast. One hour later, the patient has a light breakfast and eats normally thereafter. Urine samples are collected at 15', 30', 1 h, 2h, 3h, 4h, 5 h, 6h, 7h, 8h, 9h, 10h, 11h, and 12h intervals following dosing. The samples are weighed. A 10 ml aliquot is taken from each time point and the aliquots are stored at -20 °C. Samples (0.5 ml) are then transferred to NMR tubes spectra are taken to assess drug metabolites in urine.