TABLE 5

Distribution of radioactive metabolites in pooled plasma after an oral dose of [14C]muraglitazar to intact rats, dogs, monkeys, and humans

Metabolites are assigned based on retention times of radioactive peaks and LC/MS analysis.

Metabolite
Distribution of Muraglitazar Metabolites in Plasmaa
Rat
Dog
Monkey
Human
1 h
4 h
12 hb
 1 h
4 h
12 h
1 h
4 hb
 12 h
1 h
4 hb
 12 h
% of sample
M1 N.D.c N.D. 0.05 2.0 3.0 9.0 0.3 0.3 N.D. N.D. trace 0.2
M2 N.D. N.D. 0.05 N.D. N.D. N.D. N.D. 0.1 N.D. N.D. trace NA
M5 N.D. N.D. traced 1.0 1.0 15.0 1.5 2.9 2.7 N.D. 0.3 1.0
M6 N.D. N.D. trace N.D. N.D. N.D. N.D. trace N.D. N.D. N.D. N.D.
M8 N.D. N.D. trace N.D. N.D. N.D. 1.0 1.5 1.0 N.D. trace N.D.
M8a N.D. N.D. trace N.D. N.D. N.D. 0.9 1.3 1.0 N.D. trace N.D.
M10 N.D. N.D. 0.2 1.0 N.D. 9.0 0.9 1.6 0.4 N.D. 1.0 1.0
M11 N.D. N.D. trace trace N.D. N.D. 8.0 16.2 21.4 N.D. 0.3 N.D.
M12 N.D. N.D. trace N.D. N.D. N.D. N.D. trace 0.5 N.D. 0.2 N.D.
M13 N.D. N.D. 0.05 trace N.D. N.D. 0.1 0.2 0.1 2.5 4.2 2.5
M15 2.3 2.1 3.5 1.0 3.0 9.0 0.1 0.3 N.D. 0.2 0.5 0.4
M18 N.D. N.D. trace N.D. N.D. N.D. N.D. 3.1 4.0 N.D. 0.3 N.D.
M20 N.D. N.D. 0.4 N.D. 3.0 N.D. 0.1 0.2 0.4 N.D. N.D. N.D.
P 95.9 95.3 92.2 90.5 81.3 33.0 85.1 67.6 65.9 97.1 92.2 94.0
Othere 6.8 10.5 1.6 2.0 6.7 21.0 5.5 1.1 0.6 1.3 0.6 0.2
Total
98.2
97.4
96.6
97.5
98.0
96.0
98.1
92.9
97.1
99.8
99.0
98.1

  • ↵ a Radioactive peaks are reported as a percentage of the total radioactivity eluted from the column. Column recoveries were >98%.

  • ↵ b LC/MS analysis was performed on this plasma sample.

  • ↵ c N.D., not detected. Criteria are no discernible radioactive peak, <0.05% radioactivity, and not detected by LC/MS.

  • ↵ d trace = <0.05% radioactivity and detected by LC/MS.

  • ↵ e Other = no identified peaks.