Increase in Tolerated Dose of Isoniazid in Mice by Use of Cycloserine

Summary

The acute toxicity of isoniazid (INH) in DBA mice by gavage, LD₅₀ = 5 mg/20 g mouse, may be reduced by simultaneous administration of the antibiotic cycloserine (CS). Each of 22 mice survived a single dose of 8 mg INH with 75 mg CS (0.4 g and 3.75 g/kg respectively), or of 10 mg INH with 100 mg CS (0.5 g and 5.0 g/kg respectively). On repeated semi-weekly administration for 10 weeks, 19 of 26 mice, 73%, survived the latter mixture. Significant amounts of INH were detected in the blood plasma 72 hours after the 20th dose. In in vitro bacteriostatic tests with 4 strains of Mycobacterium tuberculosis, CS did not interfere with the activity of the INH.

Since submission of this manuscript for publication, a statement in a technical bulletin indicated that in clinical use “toxicity (of CS) is decreased and its efficacy increased” when administered with INH. (Phys. Bull., 1956, v21, 227).