Learn More
The p160 family of coactivators, SRC-1, GRIP1/TIF2, and p/CIP, mediate transcriptional activation by nuclear hormone receptors. Coactivator-associated arginine methyltransferase 1 (CARM1), a previously unidentified protein that binds to the carboxyl-terminal region of p160 coactivators, enhanced transcriptional activation by nuclear receptors, but only when(More)
One of the most effective ways in which regulatory agencies communicate with sponsors and guide drug development is through the issuance of guidances or guidelines. These can be issued domestically in a given region such as the United States by the Food and Drug Administration (FDA) or internationally through the International Conference on Harmonization.(More)
1. Pharmacokinetic drug interactions can lead to serious adverse events and the evaluation of a new molecular entity's (NME) drug-drug interaction potential is an integral part of drug development and regulatory review before its market approval. Clinically relevant interactions mediated by transporters are of increasing interest in clinical development and(More)
Drug transporters play a key role in the absorption, distribution, and elimination of many drugs, and they appear to be important determinants of therapeutic and adverse drug activities. Although a large body of data pertaining to drug transporters is available, there are few databases that inform drug developers, regulatory agencies, and academic(More)
Physiologically based pharmacokinetic (PBPK) modeling and simulation is a tool that can help predict the pharmacokinetics of drugs in humans and evaluate the effects of intrinsic (e.g., organ dysfunction, age, genetics) and extrinsic (e.g., drug-drug interactions) factors, alone or in combinations, on drug exposure. The use of this tool is increasing at all(More)
Between January 1991 and July 1992, 350 laparoscopic cholecystectomies were performed. There were six biliary complications (1.7 per cent): common bile duct (CBD) injury (one patient), delayed CBD necrosis (one), immediate postoperative bile leakage (one) and delayed bile leakage (three). All six patients required laparotomy. Primary repair with long-arm T(More)
A duodenal diverticulum (DD) appears in 2.5% of upper gastrointestinal (UGI) examinations and up to 22% of endoscopic retrograde cholangiopancreaticographies (ERCP) and autopsies. Most of these patients are asymptomatic, but the lesion is occasionally associated with bleeding, inflammation, perforation, obstruction of the duodenum or biliary-pancreatic duct(More)
1. Troglitazone was the first thiazolidinedione approved for clinical use in the treatment of non-insulin-dependent diabetes mellitus. During clinical investigations of drug-drug interactions with therapeutics (terfenadine and cyclosporine) known to be metabolized by CYP3A4, pharmacokinetic interactions were noted upon troglitazone multiple-dose treatments.(More)
BACKGROUND St John's wort (Hypericum perforatum) is a popular over-the-counter dietary supplement and herbal remedy that has been implicated in drug interactions with substrates of several cytochrome P450 (CYP) isozymes. The effect of St John's wort on CYP activity in vivo was examined with a probe drug cocktail. METHODS Twelve healthy subjects (5 female,(More)
Ethnicity is one factor that may account for the observed differences in both pharmacokinetics (PK) and pharmacodynamics (PD) of drugs, resulting in variability in response to drug therapy. Given that the applicability of clinical study results to the treatment of an individual patient is a critical consideration in a physician's choice of drug therapy,(More)