Table 5.
Effect of AR-C155858 on the oral toxicokinetics of GHB 1500 mg/kg
| GHB 1500 mg/kg oral |
GHB 1500 mg/kg oral + AR-C 5 mg/kg IV (60 min post) |
GHB 1500 mg/kg oral + AR-C 5 mg/kg IV (5 min post) |
GHB 1500 mg/kg oral + AR-C 10 mg/kg PO |
|
|---|---|---|---|---|
| AUC (mg.min/ml) |
233 (30.0) |
148* (10.7) |
124* (20.79) |
150* (5.71) |
| CL/F (ml/min/kg) |
6.52 (0.88) |
10.2* (0.75) |
12.32* (2.24) |
10.0* (0.38) |
| CLR (ml/min/kg) |
1.82 (0.63) |
5.74* (0.86) |
5.38* (0.54) |
4.95* (0.45) |
| Urinary excretion (%) |
28.2 (10.1) |
56.2* (6.84) |
44.97* (10.8) |
49.5* (5.41) |
| CLM (ml/min/kg) |
4.70 (0.99) |
4.44 (0.63) |
6.94 (2.69) |
5.07 (0.66) |
| Cmax (µg/ml) |
659 (259) |
451 (37.2) |
399 (41.4) |
300* (34.0) |
CL/F, GHB oral clearance (total clearance/bioavailability); CLR, GHB renal clearance; Cmax, maximum GHB plasma concentration; CLM, GHB non renal clearance.
GHB was administered by oral gavage. AR-C155858 (5 mg/kg) was administered as an i.v. bolus either 5 minutes or 1 hour post GHB administration. AR-C155858 (10 mg/kg PO) was also administered together with GHB by oral gavage. Data are presented as mean ± S.D., n = 4–8. One-way analysis of variance (ANOVA) followed by Tukey’s post hoc test was used to compare toxicokinetic parameters between treatment groups and GHB alone.
*
P < 0.05 compared with GHB alone.