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In open-label, randomized, three-period, three-treatment crossover studies, 10 subjects received 10 mg A, 45 mg B or the combination, while20 subjects received 20 mg A, 1000 mg C or the combination. In an open-label, randomized, five-period, five-treatment, unbalanced crossover study, 12 subjects first received 20 mg A, 4 mg D or the combination, and afterward 100 mg sitagliptin or sitagliptin plus 20 mg A. Blood samples were taken over 72 h of each treatmentperiod. Lack of PK interaction was defined as the ratio of geometric means and 90% confidence interval (CI) for combination:monotherapy being within the range of 0.80¨C1.25 ¡£
   Co-administration of A withB, C or D had no effect on A maximum plasma concentration (Cmax) or area under the plasma concentration-time curve (AUC). Similarly, A did not affect the Cmax or AUC for the co-administered drug, except for slight extensions of the 90% CI for the ratio of geometric means for B AUC (upper limit 1.29) andC Cmax (lower limit 0.75). All monotherapies and combination therapies were well tolerated.
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In open-label, randomized, three-period, three-treatment crossover studies, 10 subjects received 10 mg A, 45 mg B or the combination, while20 subjects received 20 mg A, 1000 mg C or the combination. In an open-label, randomized, five-period, five-treatment, unbalanced crossover study, 12 subjects first received 20 mg A, 4 mg D or the combination, and afterward 100 mg sitagliptin or sitagliptin plus 20 mg A¡£
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Blood samples were taken over 72 h of each treatment period. Lack of PK interaction was defined as the ratio of geometric means and 90% confidence interval (CI) for combination:monotherapy being within the range of 0.80¨C1.25 ¡£
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