Fig. 2 Mean (± standard error of the mean) plasma GLPG0259 concentrations after once-daily repeated oral dosing in fed healthy subjects: (a) dosing for 5 days (n = 6 per dose group); (b) dosing for 14 days (n = 6 per dose group). After single dosing, Cmax and AUC24h increased proportionally within the 15–100 mg and 30–150 mg dose ranges (table I). A significant dose effect on tmax was observed, with a higher median value observed at the two highest doses. Although no statistical analysis was performed on t1/2,λz, no noticeable difference in this parameter was observed, with a mean value of about 26.0 hours (range 25.5–26.4 hours). GLPG0259 Repeated-Dose Pharmacokinetics (Studies

1 and 2) GLPG0259 FK506 plasma concentration–time data are plotted in figure 2, and the pharmacokinetic parameters are listed in table II. As was already evident from the single-dose pharmacokinetics, GLPG0259 was absorbed slowly, with a trend toward an increase in tmax with increased dosing (table II).

Table II GLPG0259 pharmacokinetic parameters after once-daily repeated oral dosing in fed healthy subjects (n = 6 per dose group) The steady-state GLPG0259 plasma concentration was reached at between 4 and 8 dosing days (figure 2, table III). After the last dose, plasma elimination of GLPG0259 CP-690550 concentration over time displayed a monophasic profile, with a t1/2,λz of about 39 hours (range 35.0–41.6 hours). An approximate 2.5-fold increase in AUC24h and Cmax of GLPG0259, similar for all doses, was observed after once-daily dosing, which was consistent with the long GLPG0259 t1/2,λz. After repeated administration, GLPG0259 did not deviate from dose proportionality, with AUC24h

and Cmax increasing in proportion to the dose within Nintedanib (BIBF 1120) the 20–75 mg dose range. Overall, the between-subject variability in AUC24h and Cmax at steady state was low/moderate (between-subject CV range 16–30%) as was the within-subject variability, which was derived from the square root of the mean square error of the ANOVA (the CVs of AUC and Cmax ranged between 9.8% and 20%; data not shown). Table III Trough plasma GLPG0259 concentrations after once-daily repeated oral dosing in fed healthy subjects (n = 6 per dose group) Excretion of unchanged GLPG0259 in urine was rapid, with about 64–88% excreted within the first 12 hours (data not shown). The Ae24h of GLPG0259 represented 4.99% and 10.4% of the dose administered after single and multiple dosing, respectively, of 50 mg of GLPG0259 for 5 days (table II). The increase in the amount of GLPG0259 excreted in urine between the first and last doses mirrored the accumulation of GLPG0259 observed in plasma. As a consequence, the CLR24h remained constant between the first and last doses. At the 20 mg dose, the increase in Ae24h between the first and last doses (from 3.47% to 4.

No related posts.