• YAKHAK HOEJI
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• v.31 no.4
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• pp.204-212
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• 1987

Rifampicin is an indispensable drug along with isoniazid for the control of tuberculosis and is usually prescribed as the combination of rifampicin and isoniazid. This paper is attemtped to investigate the interaction of rifampicin and isoniazid. Isoniazid was administered orally at a dose of 30mg/kg of rabbits pretreated with rifampicin 7.5mg/kg, 15mg/kg, and 30mg/kg, respectively twice daily for 9 days. The results are as follows: The blood level and relative bioavailability of isoniazid were decreased significantly (p<0.05) by rifampicin at a dose of 15mg/kg and 30mg/kg. The renal clearance of total isoniazid and ratio of its metabolites to isoniazid were increased significantly (p<0.05) by rifampicin at a dose of 15mg/kg and 30mg/kg. It seemed to be due to enzyme induction by rifampicin. Elimination rate constant ($\beta$) of isoniazid was increased and half life ($t_{1/2$\beta}$) was decreased by rifampicin pretreatment. Dosage regimen of isoniazid after long term administration of rifampicin should be adjusted carefully.

• Tuberculosis and Respiratory Diseases
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• v.57 no.2
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• pp.180-182
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• 2004

A Case of Pellagra Induced by Isoniazid during Treatment of Pulmonary Tuberculosis Pellagra is a disease caused by a deficiency of nicotinic acid or niacin. It is mostly found among people eating corn-based diets in parts of China, Africa and India. It is also induced by drugs, such as isoniazid or 5-fluorouracil. Isoniazid inhibits the conversion of tryptophan to niacin and may induce pellagra, particularly in poorly nourished patients. Pellagra should be suspected whenever tuberculous patients under the treatment with isoniazid develop mental, neurological or gastrointestinal symptoms, even in the absence of typical skin changes. Herein, our experienced of a case of pellagra induced by isoniazid during treatment of pulmonary tuberculosis is reported. The patient was referred due to a skin rash and drowsy mental status. Her skin lesion developed during treatment for pulmonary tuberculosis. Her symptoms were improved after discontinuation of antituberculous agents and on the administration of nicotinamide.

• YAKHAK HOEJI
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• v.32 no.5
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• pp.319-327
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• 1988

Pharmacokinetic interaction of cimetidine and isoniazid was investigated in the rabbits. Isoniazid was administered orally at a dose of 30mg/kg to six rabbits after 10, 20, and 30mg/kg pretreatment of cimetidine twice a day for 10days. Concentration of the free and the total isoniazid in the blood and the urine was determined by spectrophotometer. Relative bioavailability and biological half-life($t\frac{1}{2}{\beta}$) were increased significantly by cimetidine pretreatment. Overall elimination rate constant and total clearance of isoniazid were decreased significantly by cimetidine pretreatment. The ratio of metabolites to isoniazid in the blood and the urine was decreased significantly by cimetidine pretreatment. Relative bioavailability, INAH to metabolites ratio in the blood and decrease in total clearance were highly correlated with the does of cimetidine pretreated. This result might be due to the inhibition of isoniazid metabolism in the liver by cimetidine pretreatment.

• YAKHAK HOEJI
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• v.30 no.5
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• pp.208-213
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• 1986

Rifampicin suspension was administered orally at a does of 34mg/kg to six rabbits after 5, 10 and 20mg/kg pretreatment of isoniazid twice daily for 9 days. The blood level of rifampicin was decreased significantly by isoniazid 10mg/kg 20mg/kg pretraetment. The renal clearance(CLr) of rifampicin was increased by isoniazid 20mg/kg and the biliary clearance(CLb) was incresed by isoniazid 10mg/kg and 20mg/kg pretreatmetn. Elimination rate constant(K) and time to reach maximum concentration(tmax) were increased by isoniazicl pretreatment. But half-life and maximum concentration(C max) were decreased. Relative bioavailability was decreased significantly by isoniazid 10mg/kg and 20mg/kg pretreatment.

• Korean Journal of Clinical Laboratory Science
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• v.41 no.1
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• pp.24-30
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• 2009

Rifampicin (RIF) and isoniazid (INH) are the most important drug for the treatment of Mycobacterium tuberculosis. Mutations correlated to rifampicin and isoniazid-resistance have been detected in rpoB gene and katG gene, respectively. Of the rifampicin-resistant isolates, 90% showed mutations in rpoB gene at codon 507 to 533. Isoniazid-resistant isolates analysed had a mutation in katG at codon 315. The aim of this study is to develop a pyrosequencing-based approach for rapid detection of ripampin or isoniazid resistant M. tuberculosis based on characterization of all possible mutation in the target region. For this study, the DNA selected from 35 cases of MTB PCR positive clinical sample such as bronchial washing, sputum, and pleural fluid. RIF or INH resistant was analyzed by pyrosequencing data of rpoB and katG gene. 28 (80%) and 7 (20%) of 35 MTB PCR positive DNAs were occured rifampicin-sensitivity and resistant, respectively. For INH, 30 (85.7%) and 5 (14.5%) cases were detected isoniazid-sensitivity and resistant, respectively. When pyrosequencing analysis was compared with ABI sequencing analysis, both analysis were presented same result, but pyrosequencing analysis was more rapid than ABI sequencing analysis. In conclusion, we found that pyrosequencing technology offers high accuracy, specificity, short turn around time and a high throughput in detection of rifampicin or isoniazid resistance in M. tuberculosis.

• Toxicological Research
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• v.19 no.3
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• pp.235-240
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• 2003

The modification of CYP2E1 activity is of considerable interest because of its role in the metabolic activation of a variety of toxic chemicals. In the present studies, the time-course of changes in human CYP2E1 activities was determined after treatment with ethanol, glycerol, 4-methylpyrazole or isoniazid using intact HepG2 cells transfected by human CYP2E1. Hydroxylation of chlorzoxazone was chosen for the measurement of CYP2E1 activity. CYP2E1 protein levels were increased upon cultivation of cells in the presence of ethanol, glycerol, 4-methylpyrazole or isoniazid for 24 hr. After 24 hr cultivation, ethanol or glycerol increased CYP2E1 activities, whereas 4-methylpyrazole or isoniazid inhibited. This different effect of the chemical inducers on CYP2E1 activi-ties persisted to subsequent 24 hr. Competitive inhibition study suggested that 4-methylpyrazole or isoniazid has stronger binding affinity to CYP2E1 than ethanol or glycerol. These results demonstrate that different binding affinity of the chemical inducers to the active site of CYP2E1 plays important role in determining real CYP2E1 activity in intact cells after treatment with the chemical inducers. Present study would be helpful in precise understanding of human CYP2E1-mediated toxicity.

• Tuberculosis and Respiratory Diseases
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• v.65 no.4
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• pp.308-312
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• 2008

Gynecomastia is a benign enlargement of the male breast attributable to proliferation of the ductal elements. Gynecomastia has been rarely reported as an adverse effect of isoniazid therapy. We report the case of a 35-year-old man who was prescribed with isoniazid, rifampicin, ethambutol and pyrazinamide to treat pulmonary and lymphatic tuberculosis. After five months of treatment, the patient complained of painful engorgement in the bilateral breasts and the presence of male gynecomastia was confirmed with a physical examination and radiographical methods. The serum level of estradiol was also increased. Common causes of male gynecomastia were excluded through history taking and the laboratory findings. The anti-TB drugs were changed to a second line regimen due to radiographical progression and the intolerance of the patient to gynecomastia. Gynecomastia was relieved very slowly and a tender subareolar palpable mass decreased in size and consistency over five-month period after stopping the probable causative drug, isoniazid. From a review of the literature, gynecomastia has been shown to be a side effect of treatment with first line anti-tuberculosis drugs, and especially with isoniazid. We report the rare case.

• Tuberculosis and Respiratory Diseases
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• v.56 no.4
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• pp.411-414
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• 2004

Isoniazid is a first-line drug in the treatment of tuberculosis. A variety of adverse reactions of isoniazid have been reported. These include hepatitis, peripheral neuropathy, skin rashes, neurologic disturbances and hematologic alterations. Among these, acute pancreatitis due to isoniazid is very rare. We report a case of acute pancreatitis due to isoniazid confirmed by rechallenge test with review of some literatures.

• Tuberculosis and Respiratory Diseases
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• v.66 no.1
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• pp.33-36
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• 2009

We emphasizes the fact that isoniazid could lead to the development of gynecomastia. Physicians should be aware of this rare adverse effect.

• Korean Journal of Pharmacognosy
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• v.40 no.2
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• pp.137-142
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• 2009

Isoniazid was discovered in 1950's and since then it has been widely used as a synthetic bactericidal agent in the treatment of tuberculosis. However, the adverse effect of isoniazid has been reported to show significant hepatotoxicity in approximately 1-2% of patients. Nitrofurantoin {1-(5-nitro-2-furfurylideneamino)-hydantoin} is a synthetic nitrofuran that is commonly used for the treatment and prophylaxis of urinary tract infections, but its use is associated with liver cirrhosis and fatal liver necrosis. Therefore, studies for natural products with protective effect on the isoniazid- and/or nitrofurantoin-induced hepatotoxcity would be valuable as the potential therapeutic use. 107 plants sources were collected at Mt. Baekdu, and extracted with methanol. These extracts had been screened for the protective effects against isoniazid- and/or nitrofurantoin-induced cytotoxicity in HepG2 cells at the both 100 and $300{\mu}g/ml$. Five methanolic extracts, Acanthopanax senticosus, Acer mono, Asparagus schoberioides, Fagopyrum tataricum, Potentilla centigrana, showed significant protective effects against isoniazidinduced hepatotoxicity. Two methanolic extracts, Acer mono and Leonurus artemisia, showed significant protective effects against nitrofurantoin-induced cytotoxicity in HepG2 cells.