Mean PK and PD parameters (± S.E.) for cocaine after bolus and self-administration dosing regimes in rats
| Group 1 | Group 2 | |
|---|---|---|
| 0.5 mg/kg/infusion | 1 mg/kg/infusion | |
| PK parameters | ||
| Bolus administration | ||
| V c,b(l/kg) | 2.63 ± 0.21 | 2.37 ± 0.02 |
| V ss,b (l/kg) | 4.51 ± 0.26 | 4.53 ± 0.12 |
| CLb (l/h/kg) | 7.85 ± 0.29 | 7.52 ± 0.67 |
| MRTb (min) | 34.6 ± 2.1 | 36.6 ± 2.4 |
| k 10,b (min−1) | 0.051 ± 0.006 | 0.053 ± 0.005 |
| k 12,b(min−1) | 0.040 ± 0.009 | 0.034 ± 0.006 |
| k 21,b (min−1) | 0.056 ± 0.008 | 0.037 ± 0.005 |
| αb(min−1) | 0.12 ± 0.02 | 0.11 ± 0.01 |
| t 1/2α,b (min) | 5.8 ± 0.7 | 6.8 ± 0.7 |
| βb (min−1) | 0.023 ± 0.002 | 0.019 ± 0.001 |
| t 1/2β,b(min) | 31.1 ± 3.1 | 38.0 ± 2.7 |
| AUC(0–∞),b: 0.5 mg/kg (μg · min/ml) | 3.46 ± 0.14 | 3.72 ± 0.38 |
| AUC(0–∞),b: 1 mg/kg (μg · min/ml) | 6.78 ± 0.25 | 7.14 ± 0.61 |
| AIC | −3.28 ± 0.05 | −3.04 ± 0.10 |
| Self-administration | ||
| V c,sa(l/kg) | 1.20 ± 0.07 | 1.05 ± 0.08 |
| k 10,sa (min−1) | 0.23 ± 0.02 | 0.18 ± 0.02 |
| k 12,sa(min−1) | 0.040 ± 0.009 | 0.034 ± 0.006 |
| k 21,sa (min−1) | 0.056 ± 0.008 | 0.037 ± 0.005 |
| CLsa (l/hr/kg) | 16.7 ± 2.4 | 11.3 ± 1.1 |
| αsa(min−1) | 0.28 ± 0.03 | 0.22 ± 0.03 |
| t 1/2α,sa (min) | 2.5 ± 0.2 | 3.2 ± 0.4 |
| βsa (min−1) | 0.046 ± 0.007 | 0.030 ± 0.004 |
| t 1/2β,sa(min) | 15.7 ± 2.5 | 23.7 ± 2.5 |
| AUC(0–∞),sa (μg · min/ml) | 72.6 ± 10.7 | 125.7 ± 9.6 |
| AIC | −1.23 ± 0.58 | −0.81 ± 0.57 |
| PD parameters | ||
| Number of responses | 43.7 ± 1.3 | 24.5 ± 0.6 |
| Interinfusion intervals (min) | 3.5 ± 0.1 | 6.2 ± 0.1 |
| Total doses (mg/kg) | 24.5 ± 0.8 | 27.0 ± 0.6 |
| C max (μg/ml) | 0.82 ± 0.08 | 1.47 ± 0.05 |
| C min (μg/ml) | 0.28 ± 0.06 | 0.34 ± 0.05 |
Subscript b and sa denote bolus and self-administration, respectively.