Time Saving Practices For AG-1478 ALK Inhibitor

The dose of CP 690,550 used in this present research is three times higher than the highest dose planned for Phase III research of the combination, which need to cover the extremes of exposures AG-1478 observed with all the therapeutic dose.

Greater, long term research of concomitant administration of CP 690,550 and MTX are necessary to conrm the efcacy and safety of this combination in greater patient populations and evaluate the will need for dose adjustments based on efcacy AG-1478 and/or safety data. To this end, the com bination of CP 690,550 and MTX is currently undergoing further evaluation in patients with RA. Theophylline has been used for many years to treat acute asthma and chronic obstructive pulmonary disease. Oral absorption of theophylline is almost complete, with peak plasma concentrations generally achieved 2 h after administration, although this can be inuenced by coadministered medications. The therapeutic index of theophylline is low with the therapeutic concentration ranges of 5?20 g ml1, and signs of toxicity or therapeutic failure may occur with relatively small changes in plasma concentrations of the drug.

Although some in vitro ndings have suggested that there are drug interactions between danshen VEGF extract and CYP1A2 substrates, no in vivo studies have investigated the inuence of danshen extract on theophylline metabolism. The purpose of this study was to investigate whether danshen extract can inuence CYP1A2 activity and consequently alter the pharmacokinetics of theophylline in healthy volunteers. The extract was obtained from the dried root of danshen. Danshen extract tablet used in this study was produced according to the methods of the Chinese Pharmacopoeia, which contained an extract of 1 g danshen manufactured by Shanghai Leiyong Shong Pharmaceutical Limited Company. This product had been registered for ALK Inhibitor clinical use for decades in China.

The hydrophilic and lipophilic components of Danshen extract tablet were separately determined by highperformance liquid chromatography. The Waters HPLC system, used for determination of the components of danshen, consisted of a 515 binary HPLC pump, a 717 plus autosampler, a column incubator, a 2487 ultraviolet AG-1478 detector, and Breeze Software. A Lichrospher C18 column was used for analysis. For determination of hydrophilic components, the mobile phase was 0. 5% acetic acid:methanol. Elution was carried out at a ow rate of 1 ml min1 and at a column temperature of 35 C. The detection wavelength was set to 282 nm. For determination of the lipophilic components, the mobile phase was 0. 5% acetic acid:methanol. The ow rate was 1. 0 ml min1. The detection wavelength was set to 254 nm.

The following reference standards were used: cryptotanshinone, tanshinone I, tanshinone IIA, danshensu, protocatechuic acid and salvianolic acid B purchased from the National Institute for the Control of Pharmaceutical and Biological Products. All subjects were nonsmokers and were healthy on the basis of medical history, physical examination, electrocardiogram and routine tests of urine, biochemistry and haematology.