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The dose of CP 690,550 used in this current research is three times greater than the highest dose planned for Phase III studies with the combination, which should cover the extremes of exposures AG-1478 observed with the therapeutic dose.

Bigger, long lasting studies of concomitant administration of CP 690,550 and MTX are expected to conrm the efcacy and safety of this combination in bigger patient populations and evaluate the want for dose adjustments determined by 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 HSP 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 contents of the lipophilic components in each table found were: cryptotanshinone, tanshinone I and tanshinone IIA, the contents of the major hydrophilic components were: danshensu, protocatechuic acid and salvianolic acid B. All analyses ALK Inhibitor were performed in triplicate.