TY - JOUR
T1 - Effects of cimetidine on the metabolic disposition of isoniazid in rabbits
AU - Hsu, K. Y.
AU - Uang, Y. S.
N1 - Funding Information:
The financial support of Fellowship from Universiti Sains Malaysia for Mr. Ng Kai Foon and Dr. Tan Thuan Chew was gratefully acknowledged. We gratefully acknowledge and are indebted to the anonymous referees for comments and constructive suggestions provided for improving the manuscript.
PY - 1989
Y1 - 1989
N2 - Effects of cimetidine on the metabolic disposition of isoniazid (INH) were investigated in rabbits administered with 0.109 mmol kg-1 of either INH, acetylisoniazid (AcINH), isonicotinic acid (INA), sodium α-ketoglutarate isonicotinoyl hydrazone (INH-K) or sodium pyruvate isonicotinoyl hydrazone (INH-P). Oral cimetidine (50 mg kg-1 given 1 h prior to the other drugs significantly (p <0.05) decreased the systemic clearance (CL) (mean ± SEM) of INH from 95.5 ± 18.8 to 44.9 ± 9.0 ml min-1 kg-1. The mean formation fraction (F) of INA formed from the hydrolysis of INH and AcINH after administration of INH was significantly decreased (p <0.05) from 0.345 ± 0.033 to 0.248 ± 0.023, and that of INA formed directly from INH was also significantly decreased (p <0.05) from 0.261 ± 0.0017 to 0.179 ± 0.029. However, the mean F values of AcINH, INH-K and INH-P formed from INH were not influenced by cimetidine. The mean fraction of unchanged INH was increased significantly (p <0.05) from 0.076 ± 0.060 to 0.171 ± 0.031. An inverse linear relationship (r = -0.827, p <0.05) existed between the F of INA formed directly from INH and the fraction of unchanged INH in rabbits pretreated with cimetidine, indicating that the F of INA formed directly from INH decreased as the fraction of unchanged INH increased after cimetidine pretreatment. Furthermore, the mean F of INA after i.v. administration of AcINH also decreased significantly (p <0.05) from 0.475 ± 0.037 to 0.379 ± 0.015 in rabbits pretreated with cimetidine.
AB - Effects of cimetidine on the metabolic disposition of isoniazid (INH) were investigated in rabbits administered with 0.109 mmol kg-1 of either INH, acetylisoniazid (AcINH), isonicotinic acid (INA), sodium α-ketoglutarate isonicotinoyl hydrazone (INH-K) or sodium pyruvate isonicotinoyl hydrazone (INH-P). Oral cimetidine (50 mg kg-1 given 1 h prior to the other drugs significantly (p <0.05) decreased the systemic clearance (CL) (mean ± SEM) of INH from 95.5 ± 18.8 to 44.9 ± 9.0 ml min-1 kg-1. The mean formation fraction (F) of INA formed from the hydrolysis of INH and AcINH after administration of INH was significantly decreased (p <0.05) from 0.345 ± 0.033 to 0.248 ± 0.023, and that of INA formed directly from INH was also significantly decreased (p <0.05) from 0.261 ± 0.0017 to 0.179 ± 0.029. However, the mean F values of AcINH, INH-K and INH-P formed from INH were not influenced by cimetidine. The mean fraction of unchanged INH was increased significantly (p <0.05) from 0.076 ± 0.060 to 0.171 ± 0.031. An inverse linear relationship (r = -0.827, p <0.05) existed between the F of INA formed directly from INH and the fraction of unchanged INH in rabbits pretreated with cimetidine, indicating that the F of INA formed directly from INH decreased as the fraction of unchanged INH increased after cimetidine pretreatment. Furthermore, the mean F of INA after i.v. administration of AcINH also decreased significantly (p <0.05) from 0.475 ± 0.037 to 0.379 ± 0.015 in rabbits pretreated with cimetidine.
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M3 - Article
AN - SCOPUS:0024817268
SN - 0217-9687
VL - 4
SP - 307
EP - 314
JO - Asia Pacific Journal of Pharmacology
JF - Asia Pacific Journal of Pharmacology
IS - 4
ER -