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The xed sequence design and style will be the simplest design and style to estimate the impact of both drugs on a single one more as suggested by regulatory guidance.

Greater, long term research of concomitant administration of CP 690,550 and MTX are required to conrm the efcacy and safety of this combination in greater patient populations and evaluate the will need 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.

All subjects were nonsmokers and were healthy on the basis of medical history, physical examination, electrocardiogram and routine tests of urine, biochemistry and haematology. Furthermore, all volunteers were required to have no laboratory evidence of hepatitis B, hepatitis C or human immunodeciency virus infection.