Table 3.

Summary of pharmacokinetic parameters in Part A: (A) AZD6244. (B) N-desmethyl AZD6244

(A) AZD6244
AZD6244 Hyd-Sulfate capsule doseSummary statisticDay 1 (single dose)Day 8 (twice-daily dose)
CmaxtmaxAUCt1/2CL/FVss/FCmaxtmaxAUC0-12CL/F
ng/mLHng×h/mLhL/hLng/mLhng×h/mLL/h
25 mgn6655n6655556666
Mean*3691.271,3616.9818.81264581.281,51516.7
Range268-5331.00-2.001,060-1,9105.77-8.2813.1-23.585.8-219326-6781.00-2.001,310-1,87013.3-19.0
50 mgn7766667777
Mean*1,03613,0757.22181259871.5338115.8
Range570-1,8000.50-1.501,500-6,4304.94-10.17.77-33.353.8-202532-1,4400.95-4.002,040-6,3507.88-24.5
75 mgn7733336655
Mean*1,2071.56,3355.3312.189.31,4391.495,44814.8
Range611-2,0001.00-2.025260-85103.87-7.448.82-14.252.3-115922-1,7701.00-3.982,940-7,8309.58-25.5
100 mgn8855557755
Mean*1,4831.047,0556.815.186.61,3651.584,75823.2
Range235-2,6901.00-2.104,260-12,5003.90-8.668.02-23.465.4-105856-2,6301.00-4.032,710-9,59010.4-37.0
(B) N-desmethyl AZD6244
AZD6244 Hyd-Sulfate capsule doseSummary statisticDay 1 (single dose)Day 8 (twice daily dose)
CmaxtmaxAUCt1/2CL/FVss/FCmaxtmaxAUC0-12CL/F
ng/mLhng×h/mLhL/hLng/mLhng×h/mLL/h
75 mgn7735NCNC664NC
Mean*78.11.582012.7NCNC66.61.52365NC
Range36.8-1731.00-3.95417-1,5204.60-34.3NCNC20.2-1151.00-3.98324-412NC
100 mgn8844NCNC775NC
Mean*97.31.55068.86NCNC65.31.58321NC
Range14.3-2451.00-8.00374-6965.64-10.4NCNC43.2-1871.00-4.03238-407NC

Abbreviation: NC, not calculated/non calculable.

  • *Geometric mean for Cmax, AUC and AUC0-12; arithmetic mean for t1/2, CL/F, Vss/F, median for tmax.

  • Only the 75-mg and 100-mg cohort data are presented for N-desmethyl AZD6244: at 25 mg and 50 mg the concentrations were below the assay limit of quantification prior to the terminal phase for the majority of patients, therefore AUC and t1/2 values could generally not be determined.