• YAKHAK HOEJI
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• v.19 no.4
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• pp.240-245
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• 1975

The quantitative analysis of ethambutol.2HCl as well as commercial ehambutol preparations was undertaken by gas-liquid chromatography by finding optimum conditions, such as the use of internal standard, stability of an ethambutol-2HCl-caffeine standard solution, and the effect of column temperature, N, O-bis-(trimethylsily) acetamide [B.S.A.] concentrations and other substances present in the preparations. Under the chromatiographic conditions, an ethambutol-2HCl. caffeine standard, 9 min, 30sec. The relative molar response of ethambutol.2HCl and caffeine studied was 2.08. Ethambutol.2HCl could be quantitated up to 1$\times$10$^{-8}$ moles. the possible decomposition of B.S.A. due to the moisture when tested and the incoplete reaction for silylation could be minimized.

• Tuberculosis and Respiratory Diseases
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• v.78 no.2
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• pp.125-127
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• 2015

We report a case of agranulocytosis caused by ethambutol in a 79-year-old man with pulmonary tuberculosis. He was referred for fever and skin rash developed on 21th day after antituberculosis drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide) intake. Complete blood count at the time of diagnosis of pulmonary tuberculosis was normal. On the seventh admission day, agranulocytosis was developed with absolute neutrophil count of $70/{\mu}L$. We discontinued all antituberculosis drugs, and then treated with granulocyte colony-stimulating factor. Three days later, the number of white blood cell returned to normal. We administered isoniazid, pyrazinamide, and ethambutol in order with an interval. However, fever and skin rash developed again when adding ethambutol, so we discontinued ethambutol. After these symptoms disappeared, we added rifampicin and ethambutol in order with an interval. However after administering ethambutol, neutropenia developed, so we discontinued ethambutol again. He was cured with isoniazid, rifampicin, and pyrazinamide for 9 months.

• Journal of Pharmaceutical Investigation
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• v.18 no.4
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• pp.175-180
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• 1988

The role and effect of aluminum tristearate in microencapsulation were investigated based on the dispersion system of ethambutol hydrochloride in acetone-liquid paraffin. Eudragit RS was used as a wall-forming material. Eudragit RS microcapsules prepared using aluminum tristearate were uniform, free-flowing particles. The phase diagram of ethambutol hydrochloride-Eudragit RS-aluminum tristearate indicated that spherical microcapsules ranging from 250 to 1400 ${\mu}m$ in diameter could be prepared only in a very limited region. Instrumental analysis using an energy dispersive-type X-ray microanalyser and a scanning electron microscope showed that aluminum tristearate was localized near the surface of microcapsules. From these results, it was presumed that aluminum tristearate reduced the phase tension between Eudragit microcapsules and liquid paraffin. The dissolution rates of ethambutol hydrochloride from Eudragit RS microcapsules were consideraly lower than those from ethambutol hydrochloride powders and decreased as the amount of aluminum tristearate decreased.

• Archives of Pharmacal Research
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• v.4 no.1
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• pp.1-8
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• 1981

Our need for a convenient method of analytical estimation of the precise optical purity of d-2 aminobutanol (d-2AB) and d-ethambutol has prompted us to examine in detail the preparation and G. L. C. separation of the N-TFA-L-prolyl derivatives of their optical isomers (d-and l-2AB, d-, meso-and l-ethambutol). Silicon OV-1 columns were used for the G. L. C. separation.

• Journal of Pharmaceutical Investigation
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• v.35 no.2
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• pp.123-127
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• 2005

An HPLC method was employed for the determination of ethambutol in human plasma. After addition of internal standard (IS, octylamine, $2\;{\mu}g/mL$) and alkalinization of the plasma with 5 M sodium hydroxide, the drug and IS were extracted into the mixture of chloroform and diethyl ether (40:60, v/v). Following a 15-min vortex-mixing and a 10min centrifugation, the organic phase was spiked with $100{\mu}L$ of phenylethylisocyanate $(2000{\mu}g/mL)$ for chemical derivatization, mixed for 5 min and evaporated to dryness under a stream of nitrogen. The residue was reconstituted with $100{\mu}L$ of mobile phase and $20{\mu}L$ was injected into C18 column with a mobile phase consisting of methanol:water (70:30, v/v). The samples were detected utilizing an ultraviolet detector at 200 nm. The method was specific and validated with a limit of $0.15\;{\mu}g/mL$. Intra- and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification. The applicability of this method was demonstrated by analysis of human plasma after oral administration of a single 1200-mg dose to 20 healthy subjects. From the plasma ethambutol concentration vs. time curves, the mean AUC was $9.61{\pm}1.64\;{\mu}g{\cdot}hr/mL$ and Cmax of $2.68\;{\mu}g/mL$ reached 2.73 hr after administration. The mean biological half-life of ethambutol was $3.46{\pm}1.21$ hr. Based on the results, this simple and validated assay could readily be used in any pharmacokinetic studies using humans.

• Korean Journal of Clinical Pharmacy
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• v.28 no.2
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• pp.95-100
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• 2018

Background: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that can affect many organs of the body but usually affects the lungs. The prevalence of TB in Korea is considerably higher than that in other countries with similar economic levels, and is much higher in elderly people. Pharmacotherapy is important in the treatment of TB and requires relatively high compliance for a prolonged duration. Methods: We analyzed sample data of elderly patients obtained from the Health Insurance Review and Assessment Service. We used logistic regression analysis and frequency analysis to identify factors that could affect prevalence of TB in elderly patients, compliance with prescribed medication regimes in these patients, and use of medical institutions. Korean Standard Classification of Diseases, version 7 (KCD-7) was used to diagnose pulmonary TB, and medications were analyzed using Korean standardized drug classification codes. Results: 1,276,331 patients were analyzed in the sample of the elderly population, and 16,658 TB patients were included in the study. The mean age of the TB patients was 76.19 years (SD 6.899). A total of 699 patients were prescribed isoniazid, rifampicin, ethambutol, or pyrazinamide at least once. Of these, 352 (50.4%) were prescribed all four medications and 101 (14.4%) were prescribed only isoniazid, rifampicin, and ethambutol. The mean duration of prescription was 28.75 days (SD 36.13). Conclusion: In the elderly population, old age and poor socioeconomic conditions correlated with TB prevalence. Most patients did not meet the criteria for effective pharmacotherapy of TB.

• Genomics & Informatics
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• v.21 no.3
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• pp.32.1-32.11
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• 2023

Resistance to anti-tuberculosis drugs, especially ethambutol (EMB), has been widely reported worldwide. EMB resistance is caused by mutations in the embB gene, which encodes the arabinosyl transferase enzyme. This study aimed to detect mutations in the embB gene of Mycobacterium tuberculosis from Papua and to evaluate their impact on the effectiveness of EMB. We analyzed 20 samples of M. tuberculosis culture that had undergone whole-genome sequencing, of which 19 samples were of sufficient quality for further bioinformatics analysis. Mutation analysis was performed using TBProfiler, which identified M306L, M306V, D1024N, and E378A mutations. In sample TB035, the M306L mutation was present along with E378A. The binding affinity of EMB to arabinosyl transferase was calculated using AutoDock Vina. The molecular docking results revealed that all mutants demonstrated an increased binding affinity to EMB compared to the native protein (-0.948 kcal/mol). The presence of the M306L mutation, when coexisting with E378A, resulted in a slight increase in binding affinity compared to the M306L mutation alone. The molecular dynamics simulation results indicated that the M306L, M306L + E378A, M306V, and E378A mutants decreased protein stability. Conversely, the D1024N mutant exhibited stability comparable to the native protein. In conclusion, this study suggests that the M306L, M306L + E378A, M306V, and E378A mutations may contribute to EMB resistance, while the D1024N mutation may be consistent with continued susceptibility to EMB.

• Journal of Chest Surgery
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• v.43 no.6
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• pp.716-720
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• 2010

Background: Cervical tuberculous lymphadenitis is the most common form of peripheral tuberculous lymphadenitis. The American Thoracic Society recommends 6 months of isoniazid, ritampin, ethambutol and pyrazinamide for treatment of peripheral tuberculous lymphadenifls, but even with this recommended treatment, frequent relapse occurs in actual clinical situations. Material and Method: The medical records of 38 patients diagnosed and treated for cervical tuberculous lymphadenitis between February 1997 and February 2007 were retrospectively reviewed. Result: The study included 14 males (36.8%) and 24 females (63.2%), with a mean age of $36.9{\pm}16.3$ years. The most frequent symptom was palpable neck mass in 24 patients (63.2%); 10 patients (26.3%) complained of fever or chills. Only nine patients (23.7%) had radiologic abnormalities. All patients received anti-tuberculous medications for at least 7 months, with isoniazid, rifampin, ethambutol and pyrazinamide for the first 2 months, and then isoniazid, rifampin and ethambutol given for more than 5 months. Relapse occurred in 7 patients (21.2%). Conclusion: Since many patients with cervical tuberculous lymphadenitis have no symptoms and show no radiologic abnormalities, diagnosis and treatment tend to be delayed. Considering the high relapse rate, the anti-tuberculous medication period should be longer than 6 months and this is recommended by the American Thoracic Society.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.992-1000
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• 1997

Background : Since up to 90% of a theophylline dose is biotransformed, probably by interaction with one or more the variants of the cytochrome P-450 drug metabolism system, anti-tuberculosis agents including drugs influencing microsomal enzyme systems, such as isoniazid and rifampicin. may be affect the elimination of theophylline. Method : The effect of combination therapy with isoniazid(INH), rifampicin(RFP), ethambutol(EMB) and pyrazinamide(PZA) on the pharmacokinetics of theophylline was evaluated by a computer program using Bayesian method. Three group were divided as follows. Group I is control, Group II is treated with INH. RFP, EMB and PZA and Group III is treated with INH, RFP and EMB. All of them were ilon-smoker who were normal in liver and renal functions, and not administered drugs affecting on the clearance of theophylline with exception of anti-tuberculous agents. Results : When it compared control with test groups, the clearance of theophylline in Group II and Group III was significantly decreased(p<0.001), and half life in Group II and Group III showed significant elevation(p<0.001). However there were no significant differences in clearance and half life between the Group II and Group III. Conclusion : These results suggest that theophylline dose may be need of readjustment in concurrent medication of anti-tuberculous agents including INH, RFP, and EMB.

• Tuberculosis and Respiratory Diseases
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• v.59 no.6
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• pp.619-624
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• 2005

Background : The drug resistance rate in tuberculosis patients with history of chemotherapy is an important indicator of for evaluation of appropriateness of treatment regimens and compliance of patients. This study examined the long-term changes in the drug resistance rates among TB patients failed in treatment or reactivated. Methods : The results of drug susceptibility testing data from patients registered in health centers from 1981 to 2004 were analyzed. Results : The rate of resistance to isoniazid decreased from 90% to 20%, and the resistance to ethambutol decreased from 45% to 6%. The rate of resistance to rifampicin varied from 13% to 28% and the resistance to pyrazinamide was 5% to 10%. Multidrug resistance was about 2-3% lower than any rifampicin resistance rates. The second-line drug resistance was ranged from 1% to 3%. There was no difference between patients' genders. Patient numbers per 100,000 population increased with age. The regional distribution was even at 4-6 patients per 100,000 population, and drug resistance rates were significantly lower in big city areas than in small towns and rural areas. Conclusion : The rates of resistance of Mycobacterium tuberculosis isolated from TB patients with history of chemotherapy to isoniazid, rifampin, ethambutol, and isoniazid plus rifampin were significantly decreased during over two decades.