TABLE 1.

Activities of ceftriaxone and LY333328 in rabbits ^a

Antibiotic	CmaxS (μg/ml)	CL (ml/min/kg)	t1/2β (h)	V (liter/kg)	AUCS 0–12h (mg × h/liter)	Observed CmaxCSF (μg/ml)	AUCCSF 0–12h (mg × h/liter)	AUCCSF 0–12h/ AUCS 0–12h	Change in log CFU/ml	No. of leukocytes (1/μl)	Protein concn (μg/ml)	Lactate concn (mmol/liter)	NSE concn (μg/ml)	No. of apoptotic neuronsb (1/mm2)
Ceftriaxone (n = 12), 20 mg/kg +  10 mg/kg/h	88.1 ± 19.29	3.33 ± 1.7	ND	ND	918.5 ± 510.4	9.43 ± 5.72	60.3 ± 31.4	0.072 ± 0.032	−0.34 ± 0.15	2,376 ± 1,562	4,183 ± 2,119	11.3 ± 5.5	153 ± 97	141 ± 39
LY333328
1 mg/kg (n = 5)	3.90 ± 1.51	0.58 ± 0.17	5.41 ± 0.95	0.26 ± 0.06	22.8 ± 5.6	BQL	BQL	ND	0.01 ± 0.11c	1,215 ± 1,141	7,589 ± 1,995	13.6 ± 6.3	274 ± 143	106 ± 31
2.5 mg/kg (n = 5)	10.64 ± 2.34	0.35 ± 0.07	7.77 ± 2.14	0.23 ± 0.05	76.1 ± 10.7	0.54 ± 0.19	3.39 ± 1.33	0.045 ± 0.019	−0.26 ± 0.22	1,492 ± 369	6,681 ± 3,999	13.2 ± 5.6	136 ± 99	106 ± 29
10 mg/kg (n = 10)	42.72 ± 11.92	0.41 ± 0.11	6.53 ± 1.86	0.22 ± 0.07	300.1 ± 84.8	0.76 ± 0.52	5.46 ± 4.28	0.018 ± 0.010d	−0.29 ± 0.21	2,147 ± 918	4,899 ± 2,243	14.9 ± 11	92 ± 69	121 ± 49
40 mg/kg (n = 2)	48.77, 53.18	0.93, 1.14	10.28, 7.41	0.74, 0.73	409.1, 335.4	1.36, 0.54	10.04, 2.36	0.025, 0.007	−0.51, −0.54	3,260, 3,421	5,197, 7,772	14.8, 17.6	ND	ND

^aC_maxS and C_maxCSF, maximum concentrations in serum and CSF, respectively; CL, clearance; t_1/2β, half-life at β phase; V, volume of distribution; NSE, neuron-specific enolase; ND, not determined; BQL, below quantification limit. AUC ratios were lower in LY333328-treated rabbits. LY333328 at 1 mg/kg was less active than ceftriaxone. Density of leukocytes, concentrations of protein and lactate in CSF, and parameters of neuronal damage showed no significant difference between ceftriaxone- and LY333328-treated animals. Because of the low number of observations, animals treated with 40 mg of LY333328/kg were not included in the statistical analysis. 

^bIn the dentate gyrus of the hippocampus. 

^cP < 0.05 versus ceftriaxone. 

^dP < 0.001 versus ceftriaxone.