Relative distribution of radioactivity (%) among various peaks in the radiochromatographic profiles of pooled 1-h plasma, 0- to 168-h urine, and 0- to 168-h feces after oral administration of [1′-14C]stavudine to six healthy male subjects
| Metabolitea | Retention Time | Percent Distribution in Pooled Samplesb | ||
|---|---|---|---|---|
| 1-h Plasma | 0–168-h Urine | 0–168-h Feces | ||
| % of dose | % of dose | |||
| Stavudine | 36.5 | 84.8 | 73.7 (67.2c) | 62.0 (1.9) |
| M1 | 32.1 | N.D. | 1.4 (1.3) | 20.8 (0.6) |
| M2 | 29.8 | 3.8 | 0.3 (0.3) | N.D. |
| M3 | 25.0 | N.D. | 1.4 (1.3) | N.D. |
| M4 | 22.8 | N.D. | 3.3 (3.1) | N.D. |
| Solvent frontd (containing M5) | 2–3 | 6.9 | 13.8 (13.1) | 8.8 (0.3) |
| Otherse | 4.5 | 6.1 (5.8) | 8.4 (0.2) | |
N.D., not detected.
↵a Structures of metabolites are shown in Scheme 1.
↵b The relative percentage distribution of radioactivity represents the percentage of radioactivity in each peak compared with the total radioactivity recovered from the HPLC column eluant after background subtraction. The percentage of dose for metabolites was calculated from the relative percentage distribution of radioactivity and the average percentage of the radioactive dose excreted in the urine or feces.
↵c A validated LC/MS/MS assay was used for the determination of the concentration of stavudine in human urine. The percentage of dose for stavudine in urine was calculated from the amount of stavudine in urine and dose administered.
↵d These values represent the total radioactivity eluted with solvent front. M5 eluted with the solvent front in plasma, urine, and feces. Further chromatographic separation of the radioactivity in solvent front from the 0- to 168-h pooled urine samples revealed at least five components in similar radioactivity (data not shown). Of the five components, only metabolite M5 was identified. The structures of other four components were not identified.
↵e Remaining radioactivity distributed in small amounts in various fractions throughout the radiochromatogram.