TABLE 1.

Mean (± S.D.) pharmacokinetic parameters and toxicity of l-AMT and d-AMT in dogs after oral administration of escalating doses of each enantiomer

l-AMT and l/d-AMT were orally administered separately to 40 beagle dogs (n = 4 per dose group) as described under Materials and Methods. Plasma samples were collected over a 4-h period and analyzed by LC-MS/MS. Pharmacokinetic parameters were derived from concentration vs. time profiles. Toxicity was determined as described under Materials and Methods.

Enantiomer	Dose	Cmax	AUC(0–4 h)	Tmax	Toxicity
	mg/kg	nM	nM × h	h
l	0.02	19.2 ± 1.1	51.5 ± 9.1	0.6 ± 0.3	None
l	0.08	80.8 ± 26	206 ± 100	0.9 ± 0.3	None
l	0.2	316 ± 79	845 ± 124	2.3 ± 1.3	+
l	0.8	566 ± 130	1640 ± 264	1.8 ± 0.5	++++
l	2.5	1050 ± 198	3050 ± 721	2.0 ± 0.0	++++
d	0.8	50.0 ± 34	134 ± 75	1.4 ± 0.8	None
d	2.5	174 ± 70	488 ± 214	2.5 ± 1.0	None
d	8.2	543 ± 222	1430 ± 627	3.0 ± 1.2	None
d	24.7	1560 ± 465	4450 ± 1364	1.3 ± 0.5	None
d	82.5	4350 ± 2145	11,600 ± 5253	2.0 ± 1.4	None