Drug Metabolism Letters - Volume 2, Issue 4, 2008

UDP-glucuronosyltransferase1A1 (UGT1A1) plays a key role to conjugate bilirubin and preventing jaundice, but there is no report showing the induction of human UGT1A1 (UGT1A1) by bilirubin. In this report, we show findings of the induction of the reporter gene (-3475/+14) of UGT1A1 in HepG2 cells by bilirubin at 50 μM, 100 μM, with human aryl hydrocarbon receptor (hAhR). We confirmed that induction of the reporter g Read More

We studied endogenous substrates for P-glycoprotein (P-gp) in an oxidative reaction mixture of ceramides, phospholipids, sphingolipids, or GM1-gangliosides (GM1-G). Extracts from the reaction mixture of galactocerebrosides (GalCer), sphingomyelin (SM) , lactocerebrosides (LactoCer), and asolectine (AS) with 0.3% hydrogen peroxide exhibited significant ATPase activity of P-gp of 7.6, 7.8, 5.3, and 4.7 nmol/min/mg protein, r Read More

Chemical analysis of fingerprint deposits from methadone-maintained opioid-dependent patients by UPLCMS/ MS show detectable levels of methadone and its metabolite, EDDP, demonstrating intake of the drug.

To evaluate the effect of endotoxin administration on the glucuronidation of multiple substrates in a rat model. In addition, the effect of endotoxin treatment on selected UGT mRNA levels in the liver and the kidney was also investigated. Male Sprague-Dawley rats (n= 6) received endotoxin (1.6 mg/kg) by intraperitoneal injection. The animals were sacrificed at 6, 12, 24, 48 hr after treatment, and the liver and the kidneys were h Read More

Virtual screening docking-based approach has been employed in order to select novel HIV-1 integrase (IN) potential inhibitors in large databases. Toxicity, metabolism and drug-like properties have been analyzed for the most promising compounds, using computational chemistry techniques. Results were compared and discussed with that obtained for a known HIV-1 (IN) inhibitor reported in the literature.

Andrographolide is a component of a famous traditional Chinese herbal medicine Andrographis paniculate (Burm) Nees. In this study, the metabolites of andrographolide in human urine after oral administration were investigated. Four urea adducts were isolated by chromatography methods and identified by high-resolution mass spectra, 1 D and 2D NMR spectroscopy.

An increased methadone enantiomer ratio (R/S) was associated to both nevirapine (179%, n=5) and efavirenz (36%, n=9) treatments when compared with that of controls (n=52). Additionally, in four follow-up patients, both R- and S-methadone normalized concentrations decreased (19%-93%) while R/S increased (22%-314%) following nevirapine/ efavirenz treatment. R/S decreased (42%) after non-compliance with e Read More

In probing enhancement of the transdermal delivery of the anti-psychotic drug haloperidol, five prodrugs (ethanoate, propanoate, butanoate, octanoate and decanoate) were synthesised and their relative rates of hydrolysis determined in the presence of porcine liver esterase (PLE), a model for cutaneous esterases. 1H NMR, MS and elemental analysis confirmed the successful synthesis of each prodrug in high purity, a Read More

The serum concentration of valproic acid (VPA) in epilepsy patients decreased in the administration of carbapenem antibiotics (CP), such as meropenem, panipenem, biapenem or imipenem, to a sub-therapeutic level. The liver is the key organ for the decrease of VPA concentration by CP, because it has been reported that no decrease of the VPA level by CP was found in hepatectomized rats. This effect was also shown Read More

An earlier reported population pharmacokinetic study documented limited predictability of amikacin clearance (65%) at birth. An exercise in the first month of life resulted in extended predictability (92%) with similar clearance estimates after the first postnatal days, reflecting the impact of postnatal age on clearance predictability.

Increased heme oxygenase-1 (HO-1) expression improves vascular function by decreasing superoxide and increasing antioxidant levels. We therefore examined if HO-1 induction increased serum adiponectin levels and ameliorated vascular dysfunction in Type 1 diabetes. Administration of either carbon monoxide (CORM-3) or the HO-1 inducers, Resveratrol, and cobalt protoporphyrin (CoPP), increased serum levels of adi Read More

Evidence, obtained in rodent and primate models of Parkinson's disease (PD) and in preliminary clinical trials, indicates that adenosine A2A receptor antagonists might represent a promising non-dopaminergic therapeutic tool for the treatment of PD. Recently, we have reported the biological evaluation of 8-substituted 9-ethyladenines (ANR) as new A2A receptor antagonists, three of which (ANR 82, ANR 94, and ANR 152) sho Read More