Cimetidine on the Study of Isoniazid Metabolism

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Abstract

Rabbit after oral administration Cimetidine (50 mg / kg) 1 hour after IV dosing were 0.109 (m-

ole / kg) Isoniazid (INH), or its metabolites Acetylisoniazid (AcINH), Sodiumison-

iazid pyruvate (INH-P), Sodium isoniazid α-ketoglutarate (INH-K) and Iso-

nicotinic acid (INA). High performance liquid chromatography determination of plasma concentrations of INH and its metabolite,

Discussed the linear speed of analysis of variance Metabolism of Cimetidine on INH.

The results showed that after the vote to Cimetidine, INH clearance rate of 95.5 ± 19.1 reduced to 44.9 ±

9.0 (ml / min.kg) which generates INA of INH metabolites generated lower proportion 0.345 ± 0.034

Was 0.248 ± 0.023, INH INA direct decomposition of water generated increased from 0.261 ± 0

. 017 reduced to 0.179 ± 0.023, both factors exhibited significant differences (P <0.05).

The NIH metabolic generation AcINH, INH-K, INH-P ratio is not the generation of Cimetidine.

Under the influence of the Cimetidine, INH to prototype away from the 0.075 ± 0.016 ratio increased to 0.

0.171 ± 0.031 (P <0.05), the direct hydrolysis with INH produced between the proportion of INA

Showed a good linear relationship (r =- 0.8273, P <0.05), which direct water decomposition INH

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INA of the metabolic pathways generated by inhibition, INH in order to increase the proportion of prototype disappear.

The first cast for INH metabolites, and found that INH-K, INA are the impact will not be Cimetidine; but INH-P of

Clearance rate increased from 9.1 ± 0.7 to 13.2 ± 1.0 (ml / min.kg) (P <0.05)

, Cimetidine is accelerating the effect of INH-P removal, the reasons are yet to be explored, Cimetidine

Also inhibit AcINH water decomposed INA. After the vote to AcINH, INA of generating increased from 0.476 ± 0.

037 reduced to 0.379 ± 0.015 (P <0.05). But then INH acetylation produced AcINH

Water decomposition INA impact of metabolic pathways are not seen.

From these results we can Cimetidine at 50 mg / kg, single dose on the rabbit on the amid-microsome

ase is inhibited.

English Abstract