TABLE 4

Effects of potential treatment strategies on the pharmacokinetics/pharmacodynamics of GHB (1500 mg/kg i.v.)

Data are presented as mean (SD); n = 3 to 5. Control = administration of GHB 1500 mg/kg intravenously. SCH50911 and l-lactate were administered intravenously 5 min after GHB. l-Lactate was administered as a 66 mg/kg bolus followed by a 302.5 mg/kg/h infusion for 8 h. One-way analysis of variance followed by Tukey's post hoc test was used to detect statistically significant differences in mean pharmacokinetic and pharmacodynamic parameters.

	Control	SCH50911				l-Lactate	5 mg/kg SCH50911 + l-Lactate
	Control	50 mg/kg	10 mg/kg	5 mg/kg	2.5 mg/kg	l-Lactate	5 mg/kg SCH50911 + l-Lactate
Cl, ml · kg⁻¹ · min⁻¹	5.16 (0.70)	6.17 (0.41)	6.13 (0.22)	6.13 (0.23)	6.05 (0.69)	6.40 (0.62)^{^a}	7.61 (0.062)^{^a,^b,^c}
Cl_R, ml · kg⁻¹ · min⁻¹	3.18 (0.66)	3.37 (0.038)	4.03 (0.21)	3.78 (0.36)	3.56 (0.50)	4.22 (0.63)^{^a}	5.28 (0.42)^{^a,^b}
Cl_m, ml · kg⁻¹ · min⁻¹	1.99 (0.17)	2.80 (0.52)^{^a}	2.09 (0.37)	2.35 (0.17)	2.50 (0.19)	2.19 (0.55)	2.33 (0.44)
Frequency ABEC, breaths	10500 (2700)	—^{^d}	3690 (1440)^{^a}	5500 (1440)^{^a}	8720 (513)	5470 (1550)^{^a}	3170 (957)^{^a}
Frequency E_max, breaths/min	17 (7)	—	51 (3)^{^a}	44 (6)^{^a}	33 (2)	24 (5)	45 (6)^{^a}
T_d, h	4.35 (1.3)	—	2.50 (0.20)^{^a}	3.15 (0.28)	4.62 (1.2)	2.45 (0.62)^{^a}	2.17 (0.14)^{^a}

↵a Significantly different from control (P < 0.05).
↵b Significantly different from 5 mg/kg SCH50911 alone (P < 0.05).
↵c Significantly different from l-lactate alone (P < 0.05).
↵d —, no ABEC, E_max, or T_d values could be calculated because respiration is similar to the baseline values; no significant decrease in frequency compared with baseline was observed after administration of 50 mg/kg SCH50911.