Relevant pharmacokinetic parameters for (R)-IF and (S)-IF after iv administration of IF enantiomers (40 mg/kg) to control and PB-treated rats
| Pharmacokinetic Parameters1-a | Control (N = 6)1-b | R/S1-c | Treated (N = 6) | R/S | p Value1-d | |
|---|---|---|---|---|---|---|
| C o(μM) | R | 99.6 ± 38.0 | 116 ± 43 | >0.5 | ||
| S | 103 ± 39.0 | 0.959 | 112 ± 43 | 1.03 | >0.5 | |
| α (min−1) | R | 0.173 ± 0.069 | ||||
| S | 0.183 ± 0.063 | 0.945 | ||||
| t 1/2α (min) | R | 4.65 ± 2.02 | ||||
| S | 4.29 ± 1.74 | 1.08 | ||||
| β (×10−2min−1) | R | 2.07 ± 0.311-e | 3.61 ± 0.67 | <0.01 | ||
| S | 1.68 ± 0.23 | 1.23 | 3.62 ± 0.39 | 0.991 | <0.01 | |
| t 1/2β(min) | R | 34.3 ± 5.21-e | 19.8 ± 3.6 | <0.01 | ||
| S | 41.8 ± 6.0 | 0.820 | 19.4 ± 2.1 | 1.02 | <0.01 | |
| V c(liter/kg) | R | 0.888 ± 0.385 | 0.751 ± 0.298 | >0.5 | ||
| S | 0.838 ± 0.326 | 1.05 | 0.750 ± 0.285 | 1.00 | >0.5 | |
| MRT (min) | R | 49.4 ± 7.4 | 20.6 ± 2.6 | <0.01 | ||
| S | 60.3 ± 8.5 | 0.820 | 19.9 ± 1.5 | 1.03 | <0.01 | |
| AUC (min · μM) | R | 4853 ± 19421-e | 1479 ± 556 | <0.01 | ||
| S | 6259 ± 2756 | 0.784 | 1356 ± 483 | 1.09 | <0.01 | |
| CL T(ml/min/kg) | R | 17.9 ± 6.81-e | 58.8 ± 26.6 | <0.01 | ||
| S | 14.0 ± 5.3 | 1.29 | 63.0 ± 22.3 | 0.930 | <0.01 | |
| V d ,ss(×103 ml/kg) | R | 1.20 ± 0.43 | ||||
| S | 1.24 ± 0.40 | 0.958 | ||||
| U (% of dose in 36-hr urine) | R | 13.1 ± 3.7 | 5.38 ± 0.901-e | <0.01 | ||
| S | 14.2 ± 4.3 | 0.934 | 4.22 ± 0.88 | 1.29 | <0.01 |
Values are mean ± SD.
↵1-a Co, initial concentration; MRT, mean residence time; CLT, total clearance;Vd,ss, steady-state volume of distribution;U, urinary excretion.
↵1-b The differences in all parameters between R- andS-isomers for the control and PB-treated groups were not statistically significant, except for those indicated,p = 0.02.
↵1-c R and S refer to (R)- and (S)-IF enantiomers, respectively. The differences in theR/S ratios between control and PB-treated rats were statistically significant, except for Vc andCo at p = 0.01.
↵1-d p values represent the significance levels for the differences in the parameters for R- orS-isomers between the control and treated groups.
↵1-e Significantly different from S-isomer value.