• 약학회지
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• 제19권4호
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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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• 제78권2호
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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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• 제18권4호
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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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• 제4권1호
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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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• 제35권2호
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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.

• 한국임상약학회지
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• 제28권2호
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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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• 제21권3호
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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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• 제43권6호
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• pp.716-720
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• 2010

배경: 결핵성 경부 림프절염은 말초 결핵성 림프절염의 가장 흔한 형태이다. 미국흉부학회 (American Thoracic Society)에서는 말초 결핵성 림프절염의 치료에 대해 6개월간의 isoniazid와 rifampin, ethambutol, pyrazinamide 투여를 권유하고 있으나 이런 치료에도 불구하고 결핵성 경부 림프절염의 경우는 실제 임상에서 재발하는 환자를 흔하게 볼 수 있다. 대상 및 방법: 1997년 2월부터 2007년 2월까지 본원에서 결핵성 경부 림프절염으로 진단 및 치료를 받은 38명의 의무기록을 후향적으로 분석하여 임상 양상과 치료 효과를 살펴보고자 하였다. 결과: 남자는 14명(36.8%)이었고 여자는 24명(63.2%)이었으며 평균 나이는 $36.9{\pm}16.3$세였다. 다른 특별한 증상 없이 경부의 종괴 촉지로 내원한 환자가 24명(63.2%)으로 가장 많았고 발열과 오한이 10명(26.3%)이었으며, 흉부 방사선 검사상 이상 소견을 보인 환자는 9명(23.7%)에 불과하였다. 모든 환자는 첫 2개월간 isoniazid, rifampin, ethambutol, pyrazinamide의 투여와 5개월 이상의 isoniazid, rifampin, ethambutol을 투여 받아 최소 7개월 이상의 항결핵제를 투여 받았다. 추적관찰 기간 중 7명(21.2%)의 환자에서 재발이 관찰되었다. 결론: 결핵성 경부 림프절염은 대부분의 환자에서 증상이 없고 방사선 검사상에서도 이상 소견을 보이지 않기 때문에 진단과 치료가 늦어지는 경향이 있다. 항결핵제의 투여에도 불구하고 비교적 높은 재발률을 고려할 때, 미국흉부학회에서 권장하는 6개월간의 치료보다는 더 장기간의 치료가 필요할 것으로 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제44권5호
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• pp.992-1000
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• 1997

연구배경 : Theophylline은 간세포내 cytochrome P-450 계열의 효소에 의해 거의 90% 정도 대사되는데, isoniazid, rifampicin 등 항결핵제틀은 미소체 효소계(microsomal enzyme system)에 영향을 미치어 theophylline과의 병용투여시 theophylline 대사에 변화를 일으킬수 있다. 방 법 : INH, RFP, EMB 및 PZA의 병합 요법이 theophylline의 약물동태에 미치는 영향에 대하여 Bayesian 방법을 이용하여 평가하였다. Theophylline을 투여중인 환자를 대상으로 3군으로 나누어, Group I를 대조군으로 하였으며, Group II는 INH, RFP, EMB 및 PZA를 병용 투여하였고, Group III는 INH, RFP 및 EMB을 병용 투여하였다. 모든 대상환자는 비흡연자로 간기능 및 신기능 검사상 정상 범위였으며 theophylline의 약물동태에 영향을 줄 수 있을 만한 약제를 복용한 환자는 제외하였다. 결 과 : 정상 대조군과 실험군들을 비교시, theophylline 소실률은 Group II와 Group III 모두 유의하게 감소하였으며(p<0.001), theophylline 반감기 역시 Group II와 Group III 모두 유의하게 증가하였다 (p<0.001). 그러나 Group II와 Group III간의 theophylline 소실률 및 반감기는 차이가 없었다. 결 론 : 이상의 결과로 INH, RFP 및 EMB 등의 항결핵제와 theophylline 병용 투여시 theophylline 용량의 재조정이 필요할 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제59권6호
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• pp.619-624
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• 2005

연구배경 : 치료 경력이 있는 환자의 약제 내성은 진료의사의 처방의 적절성 및 환자의 복용 순응도를 복합적으로 나타내어 주는 지표가 될 수 있으므로, 우리나라에서 재치료 대상 결핵 환자에서 장기간의 약제내성률 추이를 파악하고자 하였다. 방 법 : 연도별 보건소 등록환자의 약제감수성 검사 결과 및 결핵연구원의 전산 입력된 자료를 활용하여 1981년부터 2004년 사이에 주요 약제에 대한 내성률의 변화를 분석하였다. 결 과 : Isoniazid 내성은 90%에서 20%로 감소하였다. Ethambutol 내성률도 45%에서 6%로 감소하였다. Rifampin 내성률은 13%에서 28%까지 증가하다가 13%까지 감소하였다. 다제내성률은 rifampin 내성률보다 약 2-3% 낮았다. Pyrazinamide 내성률은 5% 미만에서 10% 정도까지 증가하였다가 다시 5%까지 감소하였다. 2차약제에 대한 내성률은 1-2% 정도였다. 내성 빈도는 남녀 간에 차이가 없었으며, 대도시 지역이 중소도시/농촌지역보다 낮은 약제 내성률을 보였다. 결 론 : 우리나라보건소에 등록되는 재치료 대상 결핵 환자의 주요 항결핵 약제에 대한 내성률은 2004년을 기준으로 isoniazid 20%, rifampin 13%, 다제내성 11%, ethambutol 6%, pyrazinamide 5% 기타 2차 항결핵제에 1-3%로 나타났으며 1981년 이후 모든 항결핵 약제에서 그 내성률이 유의하게 감소하고 있었다.