In vitro metabolism of methadone was investigated in cytochrome P450 (CYP) supersomes and phenotyped human liver microsomes (HLMs) to reconcile past findings on CYP involvement in stereo-selective metabolism of methadone. Racaemic methadone was used for incubations; (R)- and (S)-methadone turnover and (R)- and (S)-EDDP formation were determined using chiral liquid chromatography-tandem mass spe...

The wrist is increasingly being used as the preferred site for objectively assessing physical activity but the relative accuracy of processing methods for wrist data has not been determined. OBJECTIVE This study evaluates the validity of four processing methods for wrist-worn ActiGraph (AG) data against energy expenditure (EE) measured using a portable metabolic analyzer (OM; Oxycon mobile) a...

A higher throughput method of screening for the inhibition of recombinant CYP2D6 using a microtiter plate (MTP) assay was evaluated using 62 new chemical entities and compared to data from the dextromethorphan O-demethylase assay in human liver microsomes (HLM). The IC50 values for the two assays closely matched for 53 compounds (85%). Six of the variant nine compounds had higher IC50 values wi...

Time-dependent inhibition (TDI) of the cytochrome P450 (P450) family of enzymes is usually studied in human liver microsomes (HLM) by investigating whether the inhibitory potency is increased with increased incubation times. The presented work was initiated after a discrepancy was observed for the TDI of an important P450 enzyme, CYP3A4, during early studies of the investigational drug compound...

To lower the possibility of late-stage failures in the drug development process, an up-front assessment of absorption, distribution, metabolism, elimination, and toxicity is commonly implemented through a battery of in silico and in vitro assays. As in vitro data is accumulated, in silico quantitative structure-activity relationship (QSAR) models can be trained and used to assess compounds even...

الشاهين (محمد ميرزا بن عباس وناصر الدين ميرزا) فبدأت الحكومة بإقامة علاقة غريبة مع رجال وعلى الرغم من ان تظاهرت بدعمها للرجال الا انها فشلت في النهاية اقامة معهم، وذلك بسبب تطرف الذين لا يؤمنون بتعاليم الإسلام، وكان الصعوبة التوافق بين ورجال اثر ذلك ظهرت العديد التمردات الدينية ضد الفارسية خلال المدة (١٨٣4-١٨52م) .

Sulfadiazine hydroxylamine has been postulated to be the mediator of the greatly increased rates of adverse reactions to sulfadiazine experienced by people with human immunodeficiency virus infection. Therefore, we investigated the in vitro human cytochrome P450 (P450) and N-arylamine acetyltransferase (detoxification) metabolism of sulfadiazine. Formation of both the hydroxylamine and 4-hydrox...

Time-dependent inhibition (TDI) of the cytochrome P450 (P450) family of enzymes is usually studied in human liver microsomes (HLM) by investigating whether the inhibitory potency is increased with increased incubation times. The presented work was initiated after a discrepancy was observed for the TDI of an important P450 enzyme, CYP3A4, during early studies of the investigational drug compound...

Nicotine, the major addicting agent in tobacco and tobacco smoke, undergoes a complex metabolic pathway, with approximately 22% of nicotine urinary metabolites in the form of phase II N-glucuronidated compounds. Recent studies have shown that UGT2B10 is a major enzyme involved in the N-glucuronidation of several tobacco-specific nitrosamines. In the present study, microsomes of UGT2B10-overexpr...