Age-related changes in TRZ biotransformation in male rat hepatic and intestinal microsomes
Values are expressed as mean ± S.E. Vmax is expressed as nanomoles per minute per milligram of protein; Km is expressed in micromolar concentration, and CLint is intrinsic clearance [(Vmax/Km) · 1000]. No significant age-related differences were found for intestinal samples.
Pharmacokinetic Parameters | Young (n = 10) | Intermediate (n = 10) | Old (n = 8) |
|---|---|---|---|
| Hepatic microsomes | |||
| α-OH-TRZ | |||
| V max a | 0.29 ± 0.010 | 0.22 ± 0.014 | 0.12 ± 0.018 |
| K m b | 27.36 ± 2.35 | 20.97 ± 2.06 | 10.06 ± 1.72 |
| CLint | 11.44 ± 0.97 | 10.86 ± 0.45 | 13.68 ± 2.10 |
| Percentage of net CLint | 19% | 22% | 46% |
| 4-OH-TRZ | |||
| V max a | 0.97 ± 0.043 | 0.79 ± 0.062 | 0.25 ± 0.095 |
| K m | 21.08 ± 1.37 | 20.51 ± 1.29 | 16.27 ± 2.35 |
| CLintc | 47.26 ± 2.64 | 38.51 ± 1.96 | 15.99 ± 4.79 |
| Percentage of net CLint | 81% | 78% | 54% |
| Net CLint | 58.70 ± 3.27 | 49.37 ± 2.11 | 29.67 ± 5.05 |
| Intestinal microsomes | |||
| α-OH-TRZ | |||
| V max | 0.28 ± 0.031 | 0.25 ± 0.032 | 0.26 ± 0.059 |
| K m | 147 ± 30 | 142 ± 14 | 134 ± 20 |
| CLint | 2.27 ± 0.27 | 1.97 ± 0.37 | 2.21 ± 0.50 |
| Percentage of net CLint | 36% | 35% | 35% |
| 4-OH-TRZ | |||
| V max | 0.60 ± 0.057 | 0.49 ± 0.061 | 0.49 ± 0.101 |
| K m | 173 ± 36 | 154 ± 14 | 160 ± 37 |
| CLint | 4.08 ± 0.56 | 3.62 ± 0.73 | 3.94 ± 1.00 |
| Percentage of net CLint | 64% | 65% | 64% |
| Net CLint | 6.35 ± 0.82 | 5.59 ± 1.10 | 6.15 ± 1.49 |
↵ a Significant difference of the young from the intermediate and old groups (Kruskal-Wallis ANOVA, p < 0.001; Dunn's test, p < 0.05).
↵ b Significant difference among all age groups (ANOVA, p < 0.001; Student-Newman-Keuls test, p < 0.05).
↵ c Significant difference of the old from the young and intermediate groups (ANOVA, p < 0.001; Student-Newman-Keuls test, p < 0.05).