Table 2.
Toxicokinetics of intravenous GHB with and without AR-C155858 treatment
| GHB 200 mg/kg |
GHB 200 mg/kg + AR-C 1 mg/kg |
GHB 600 mg/kg |
GHB 600 mg/kg + AR-C 0.1 mg/kg |
GHB 600 mg/kg + AR-C 1 mg/kg |
GHB 600 mg/kg + AR-C 5 mg/kg |
GHB 1500 mg/kg |
GHB 1500 mg/kg + AR-C 1 mg/kg |
GHB 1500 mg/kg + AR-C 5 mg/kg |
|
|---|---|---|---|---|---|---|---|---|---|
| AUC (mg.min/ml) |
26.2 (0.90) |
13.3* (0.52) |
102 (12.4) |
71.3* (3.23) |
47.8* (6.58) |
52.8* (2.85) |
288 (39.8) |
170* (13.3) |
160* (17.4) |
| CLT (ml/min/kg) |
7.60 (0.29) |
15.0* (0.61) |
6.00 (0.74) | 8.42* (0.38) |
13.4* (1.98) |
11.4* (0.60) |
5.16 (0.70) |
9.25* (0.75) |
9.42* (0.98) |
| CLR (ml/min/kg) |
0.44 (0.20) |
4.41* (0.68) |
1.68 (0.75) |
3.87* (0.29) |
6.58* (0.41) |
6.38* (0.79) |
3.18 (0.66) |
7.09* (0.94) |
7.44* (1.07) |
| CLM (ml/min/kg) |
7.15 (0.45) |
10.6* (0.68) |
4.31 (0.34) |
4.56 (0.31) |
6.82* (1.58) |
5.00 (1.04) |
1.99 (0.16) |
2.16 (0.29) |
1.98 (0.22) |
| Urinary recovery (%) |
5.90 (2.86) |
29.4* (4.17) |
27.3 (9.77) |
45.9* (2.25) |
49.5* (4.00) |
56.2* (7.55) |
61.1 (5.02) |
76.4* (4.26) |
78.8* (3.98) |
GHB (200 mg/kg, 600 mg/kg, and 1500 mg/kg) was administered as an i.v. bolus with or without AR-C155858 (0.1, 1 or 5 mg/kg). AR-C155858 was administered 5 minutes after GHB administration. Data presented as mean (SD), n=4–6. One way analysis of variance followed by Tukey’s post-hoc test (GHB 600 and 1500 mg/kg) or Student’s t-test (GHB 200 mg/kg) was used to determine statistically significant difference between treatment groups.
*
P < 0.05 significantly different from their respective GHB alone group.