Amelioration of hepatotoxicity by biocleavable aminothiol chimeras of isoniazid: Design, synthesis, kinetics and pharmacological evaluation

Table 1 Doses of test and standard drugs

S.N.	Compound	Dose1, mg/kg/per day
1	H	0.9% saline (1 mL)
2	INH	150
3	NI	309
4	MGI	311
5	MI	293
6	INH + NAC	150 + 159
7	INH + MPG	150 + 161
8	INH + Met	150 + 143

¹All doses were calculated on an equimolar basis to the dose of INH. H: Healthy control; INH: Isoniazid; NI: Prodrug of INH and N-acetyl cysteine; MGI: Prodrug of INH and N-(2-mercaptopropionyl) glycine; MI: Prodrug of INH and L-methionine; INH + NAC: Physical mixture of INH+N-acetyl cysteine; INH + MPG: Physical mixture of INH + N-(2-mercaptopropionyl) glycine; INH + Met: Physical mixture of INH and L-methionine.

Table 2 In vitro release kinetics data

Prodrug	Incubation medium
	HClbuffer,pH 1.2	Phosphatebuffer,pH 7.4	Stomach homogenates	Intestinal homogenates
				K ± SD,min-11	t1/2,min	% Prodrug hydrolysed	% INH released
NI	Stable	Stable	Negligible	3.4 × 10-3	233.42	94.93	46.10
MGI	Stable	Stable	Negligible	3.3 × 10-3	217.34	70.11	33.83
MI	Stable	Stable	Negligible	5.1 × 10-3	181.36	86.55	44.26

¹Average of three readings; follows first-order kinetics.