Effects of combined d-mannitol (0.5 g/kg i.v. bolus) and lactated Ringer's solution (300 μl/min i.v. infusion) on GHB toxicokinetics and toxicodynamics
GHB (1000 mg/kg) was administered by i.v. bolus. Saline or lactated Ringer's solution was administered by i.v. infusion at the rate of 300 μl/min for 4 h. d-Mannitol (0.5 g/kg) was administered by i.v. bolus. For the combined treatment group, lactated Ringer's solution was administered by i.v. infusion (300 μl/min) for 4 h, and d-mannitol (0.5 g/kg) was administered by i.v. bolus. One-way ANOVA followed by Dunnett's test was used to detect statistical significance, n = 3 to 4, mean ± S.D.
Control | d-Mannitol (0.5 g/kg) | Lactated Ringer's Solution (300 μl/min) | d-Mannitol and Ringer's Solution | |
|---|---|---|---|---|
| AUC [GHB] (mg ml−1 min) | 109 ± 24.1 | 77.5 ± 9.24 | 83.5 ± 13.5 | 69.6 ± 1.00* |
| Total clearance (ml/h/kg) | 569 ± 113 | 781 ± 87.3* | 733 ± 120 | 862 ± 12.3** |
| Renal clearance (ml/h/kg) | 215 ± 64.9 | 356 ± 25.6* | 329 ± 85.0 | 378 ± 8.61* |
| Metabolic clearance (ml/h/kg) | 355 ± 56.6 | 425 ± 64.8 | 404 ± 41.0 | 484 ± 19.6* |
| GHB fe (%) | 37.2 ± 5.17 | 45.8 ± 2.62 | 44.4 ± 4.83 | 43.8 ± 1.53 |
| LRR (min) | 3 ± 1 | 4 ± 1 | 7 ± 3 | 13 ± 2** |
| RRR (min) | 131 ± 40 | 93 ± 3 | 93 ± 17 | 75 ± 3* |
| Sleep time (min) | 128 ± 41 | 89 ± 4 | 86 ± 20 | 62 ± 2* |
| CRRR (mg/ml) | 0.322 ± 0.052 | 0.315 ± 0.040 | 0.315 ± 0.014 | 0.352 ± 0.005 |