برای دستیابی به مزیت رقابتی در شرایط عدم‌­اطمینان که آن تغییر ضروری است، یکی از چالش‌های بزرگ سازمان‌ها کاهش ریسک طریق ایجاد زنجیره‌های تأمین تاب‌آور است. تاب‌آوری زنجیره ‌تأمین توانایی مقابله با اختلال اشاره دارد یک رویداد غیرقابل‌پیش‌بینی بوده و دارای منابع داخلی خارجی مختلفی ازجمله بلایای طبیعی ریسک‌های عملیاتی پژوهش حاضر شبیه‌سازی توسط نرم‌افزار ارنا زنجیره‌ سنگ ساختمانی «کارخانه سنگبری آسم...

AIMS The objective of this study was to evaluate the potential uses of relative abundance, relative activity approaches and inhibitory monoclonal antibodies (mAbs) in the characterization of CYP enzymology in early drug discovery. METHODS Intrinsic clearance estimates for the oxidation of ethoxyresorufin (a selective probe of CYP1A2 activity), tolbutamide (CYP2C9), S-mephenytoin (CYPC19), dex...

This study aimed to establish a practical and simplified method of predicting intestinal availability in humans (F(g,human)) at the drug discovery stage using in vitro metabolic clearance values and permeability clearance values. A prediction model for F(g,human) of 19 CYP3A substrates and 5 UGT substrates was constructed based on the concept that the permeability clearance values mean the perm...

Wushanicaritin, a natural polyphenol compound, exerts many biological activities. This study aimed to characterize wushanicaritin glucuronidation by pooled human liver microsomes (HLM), human intestine microsomes and individual uridine diphosphate-glucuronosyltransferase (UGT) enzyme. Glucuronidation rates were determined by incubating wushanicaritin with uridine diphosphoglucuronic acid-supple...

Desloratadine (Clarinex), the major active metabolite of loratadine (Claritin), is a nonsedating antihistamine used for the treatment of seasonal allergies and hives. Previously we reported that the formation of 3-hydroxydesloratadine, the major human metabolite of desloratadine, involves three sequential reactions, namely N-glucuronidation by UGT2B10 followed by 3-hydroxylation by CYP2C8 follo...

In this study we have evaluated the application and reliability of using fluorescence (FLUO)-based high throughput screening assays with recombinant CYPs (rCYP). This was accomplished by screening 29 clinically important antiparasitic drugs for inhibition of the five major drug-metabolizing CYPs (-1A2, -2C9, -2C19, -2D6, and -3A4). Data from FLUO/rCYP assays were compared with that obtained by ...

BACKGROUND: Cranberry products have been implicated in several case reports to enhance the anticoagulant effect of warfarin. The mechanism could involve inhibition of the hepatic CYP2C9-mediated metabolic clearance of warfarin by components in cranberry. Because dietary/natural substances vary substantially in bioactive ingredient composition, multiple cranberry products were evaluated in vitro...

Brivanib alaninate, the L-alanine ester prodrug of brivanib, is currently being developed as an anticancer agent. In humans, brivanib alaninate is rapidly hydrolyzed to brivanib. Prominent biotransformation pathways of brivanib included oxidation and direct sulfate conjugation. A series of in vitro studies were conducted to identify the human esterases involved in the prodrug hydrolysis and to ...

OBJECTIVE The present study explored pathways from the personality traits of neuroticism and conscientiousness through health-related behaviors to diurnal patterns of the stress hormone cortisol using data from a large national study. METHOD Using prospective data from the Midlife in the United States (MIDUS II) study and the National Study of Daily Experiences (NSDE II, a MIDUS substudy), hi...

Amlodipine is a commonly prescribed calcium channel blocker for the treatment of hypertension and ischemic heart disease. The drug is slowly cleared in humans primarily via dehydrogenation of its dihydropyridine moiety to a pyridine derivative (M9). Results from clinical drug-drug interaction studies suggest that CYP3A4/5 mediate metabolism of amlodipine. However, attempts to identify a role of...