Means of Increasing the Tolerated Dose of Isoniazid in Mice. II. Certain Amino Acids

Abstract

Summary and Conclusions

Twenty-six amino acids have been tested for their ability to reduce the toxic effect of isoniazid (INH) in mice. Eleven of these—L-cysteine-HCl. L-glutamic acid-HCl, L-histidine-HCl, L-as-partic acid, hydroxy-L-proline, L-ornithine-diHCl, acetyl-DL-methionine, L-arginine-HCl, DL-aspartic acid, L-serine, and DL-ornithine-HCl—in appropriate concentration (a 5:1 molar ratio) permitted at least 50% survival of DBA mice given an 8 mg lethal dose of INH per 20-g mouse (400 mg/kg). Optimal results were obtained with single or repeated administration of 58 mg of L-cysteine-HCl (2900 mg kg) with 8 mg INH. This dosage yielded a maximum blood plasma level of 7.8 mg% 1 hour after administration, as contrasted with 6.5 mg% following a 5 mg dose of INH alone. No interference by 4 amino acids, L-cysteine-HCl, L-glutamic acid-HCl, DL-serine, or acetyl-DL-methionine, was noted in the INH bacteriostatic test on one strain of avirulent Mycobacterium B103. From this study it would appear that L-cysteine-HCl, and perhaps other amino acids, are as effective as glycine and sodium glucuronate, previously reported, in increasing the tolerated dose of INH in DBA mice.