• Archives of Pharmacal Research
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• 제24권2호
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• pp.100-104
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• 2001

Differential pulse polarographic(DPP) analytical procedure for the rifampicin antibiotic, which can be applied to monitor its synthetic process from the starting antibiotic of rifamycin B or rifamycin SV has been developed based on the electrochemical reduction of an azomethine group. Rifampicin exhibited a cathodic peak due to the azomethine group in the side chain of 3-[(4-methyl-1-piperazinyl)imino]methyl moiety and another cathodic peak due to the carbonyl group in rifamycin SV by DPP. The experimental peak potential shift of an azomethine reduction was -73 mV/pH in the pH range between 3.0 and 7.5, agreeing with involvement of 4 e-and 5 $H^5$ in its reduction. By the cyclic voltammetric(CV) studies, the azomethine and the carbonyl reductions in rifampicin were processed irreversibly on the mercury electrode. The plot of peak currents vs. concentrations of rifampicin ranging $1.0{\times}10^{-7} M~$1.0{\times}10^{-5} M yielded a straight line with a correlation coefficient of 0.9996. The detection limit was $1.0{\times}10^{-8} M with a modulation amplitude of 50 mV DPP has been successfully applied for the determination of rifampicin in the pharmaceutical preparations.

• 약학회지
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• 제30권5호
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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.

• Tuberculosis and Respiratory Diseases
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• 제45권4호
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• pp.714-722
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• 1998

연구배경: Rifampicin은 항결핵 단기요법의 근간이 되는 약제로 rifampicin 내성용 다제내성의 지표이기도 하다. rpoB유전자는 rifampicin이 결합하여 약리작용을 나타내는 RNA polymerase의 $\beta$-subunit을 coding하는 유전자이며 rifampicin내성 결핵균의 약 96%에서 돌연변이가 관찰된다. 그러므로 rifampicin내성결핵을 빠르게 진단할 수 있는 유용한 방법을 확인하기 위하여 PCR-line probe법과 PCR-SSCP법을 이용하여 다음의 연구를 시행하였다. 방 법: 대한 결핵연구원의 약제감수성검사상 rifampicin 내성인 결핵균주 33예와 감수성인 결핵균주 12예를 대상으로 하였다. 각각 배양균 집락에서 DNA를 분리한 후, PCR-line probe법과 PCR-SSCP법을 이용하여 rifampicin 내성 여부를 단일맹검적으로 검사하였고, 이를 약제감수성검사 결과와 비교하였다. 결 과: PCR-line probe법으로는 내성균주 33예중 27예(81.8%)에서 rpoB 유전자의 돌연변이를 확인할 수 있었고, 감수성균주 12예는 모두 rpoB 유전자의 돌연변이는 없었다. PCR-SSCP 법으로는 내성균주 33예중 23예(69.7%)에서 rpoB 유전자의 돌연변이를 확인할 수 있었고, 감수성균주 12예는 모두 rpoB 유전자의 돌연변이는 없었다. Rifampicin내성균주에서 rpoB 유전자 돌연변이 검출율의 PCR-line probe 법과 PCR-SSCP법간의 차이는 없었다 (p=0.25). 결 론: PCR-line probe법은 PCR-SSCP법과 더불어 rifampicin 내성을 조기에 진단할 수 있는 좋은 방법으로 사료되며, 전통적인 약제감수성검사 결과를 기다릴 수 없는 국한된 환자에게 유용한 진단법으로 생각된다.

• 대한임상검사과학회지
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• 제41권1호
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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.

• 약학회지
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• 제40권3호
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• pp.351-356
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• 1996

The preparation of Enterococcus faecalis RSI is used as a therapeutics for human intestinal disorders. However, the microbe in this preparation is usually very sensitive to rifampicin and fluoroquinolones. If this preparation is taken with rifampicin or fluoroquinolones, its therapeutic effect can not be expected. E. faecalis RFR11, containing resistance to rifampicin was obtained by MNNG mutation method. Serial passage of E. faecalis RFR11 produced E. feacalis OFR16 on agar with 2-fold minimal inhibitory concentration of ofloxacin produced. E. feacalis OFR16 was resistant to fluoroquinolones up to 8-256 fold higher than that for the original strain. E. faecalis OFR16 also exhibited identical characteristics with the parent strain when they were tested for lactic acid formation and growth inhibition of E. coli MB4-5737 and Shigella sonnei MB4-10411. From in vitro test, it was identified that rifampicin and ofloxacin is not inactivated by certain factors of E. faecalis OFR16. Conclusively. E. faecalis OFR16, rifampicin and fluoroquinolones resistant mutant, is an efficient strain that has insensitivity against rifampicin and fluoroquinolones and original biochemical characteristics of the parent strain.

• 약학회지
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• 제38권6호
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• pp.763-769
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• 1994

Bifidobacterium bifidum, one strain of medical preparation being on the market for human intestinal disorders, was sensitive to rifampicin and fluoroquinolones. If this preparation is taken with rifampicin and fluoroquinolones, its therapeutic effect can't be expected. Serial passage of B. bifidum RFR61, which was obtained by MNNG mutation method, on agar with 2-fold minimal inhibitory concentration of ofloxacin produced B. bifidum OFR9 with minimal inhibitory contentrations of fluoroquinolones up to $4{\sim}256-fold$ higher than that for the original strain. B. bifidum OFR9 produced almost the same amount of organic acid as parental strain. This strain showed growth inhibitory activity against E. coli NM522, Shigella dysenteriae ATCC9752 and E. coli 078. No inactivations of rifampicin and ofloxacin by this resistant mutant strain were found.

• 약학회지
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• 제23권2호
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• pp.81-94
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• 1979

Rifampicin-polyvinylpyrrolidone coprecipitates were prepared by the solvent method to increase the solubility and dissolution rate, thereby improving absorption of rifampicin. It was found that the solubility and dissolution rate were greater with the 1 : 5 (w/w) coprecipitate than with the pure drug, physical mixtures or coprecipitates of any other ratio of the two components. The blood concentration data in non-fasted rats showed that the extent of absorption of rifampicin were significantly enhanced following the oral administration of the 1 : 5 coprecipitate; The area under the serum concentration curve (0-8hr) was 1.3 times greater with the 1 : 5 coprecipitate than with the pure drug. The blood concentration reached its peak (4. 38$\pm$1.36mcg/ml) within two hours in the case of oral administration of the 1 : 5 coprecipitate and, on the other hand, it reached the maximum (3.77$\pm$0.90mcg/ml) after four hours of oral administration of the pure drug. It was observed that there was no significant difference between the 1 : 5 coprecipitate and the pure drug in the extent and rate of absorption of rifampicin when fasted rats were used. When the 1 : 5 coprecipitate was orally administered to human subjects 20 minutes after meal, it was found that the blood concentration reached the maximum after one hour; in the case of the pure drug, it reached its peak after four hours.

• Journal of Microbiology and Biotechnology
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• 제11권2호
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• pp.259-265
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• 2001

Staphylococal infection still remains to be one of the most serious infections, having various complications in the clinical use of indwelling polymeric medical devices. However, there are a few promising systems showing a high antibacterial effect without causing any demage of polymer backbone under biological environments such as blood or body fluid. In order to resolve this problem, we have designed a new antibiotic releasing system via a hydrolysis mechanism. The surface of biomedical polyurethane (PU) was modified by using 1,6-diisocyanatohexane (HMDI) to immobilize the rifampicon. Also, the immobilized rifampicin was designed to be released by a selective cleavage of the unstable carbamate linkage that exists on the rifampicin-immobilized polyurethane (PHR). The immobilization of rifampicin on the surface of polyurethane was confirmed by the disappearance of the characteristics IR absorbance peak of the isocyanate (-NCO) group at $2,267\;cm^{-1}$. The PHR showed a continuous rifampicin release profile under an aqueous environment of 10 mM of PBS (phosphate-buffered saline) for ove 6 days. The rifampicin molecules, which are released from PHR under an optimal bacterial infection environment, had a higher antibacterial activity against both S. aureus and S. epidermidis than rifampicin-incorporated polyurethane (RIP). In addition, the PHR maintained a stable antibacterial effect under a blood-mimic aqueous environment such as bovine calf serum.

• Journal of Microbiology and Biotechnology
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• 제33권2호
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• pp.167-179
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• 2023

The rifampicin-resistant strain E9-302 of Edwardsiella ictaluri strain 669 (WT) was generated by continuous passage on BHI agar plates containing increasing concentrations of rifampicin. E9-302 was attenuated significantly by 119 times to zebrafish Danio rerio compared to WT in terms of the 50% lethal dose (LD₅₀). Zebrafish vaccinated with E9-302 via intraperitoneal (IP) injection at a dose of 1 × 10³ CFU/fish had relative percentage survival (RPS) rates of 85.7% when challenged with wild-type E. ictaluri via IP 14 days post-vaccination (dpv). After 14 days of primary vaccination with E9-302 via immersion (IM) at a dose of 4 × 10⁷ CFU/ml, a booster IM vaccination with E9-302 at a dose of 2 × 10⁷ CFU/ml exhibited 65.2% RPS against challenge with wild-type E. ictaluri via IP 7 days later. These results indicated that the rifampicin-resistant attenuated strain E9-302 had potential as a live vaccine against E. ictaluri infection. A previously unreported amino acid site change at position 142 of the RNA polymerase (RNAP) β subunit encoded by the gene rpoB associated with rifampicin resistance was identified. Analysis of the whole-genome sequencing results revealed multiple missense mutations in the virulence-related genes esrB and sspH2 in E9-302 compared with WT, and a 189 bp mismatch in one gene, whose coding product was highly homologous to glycosyltransferase family 39 protein. This study preliminarily explored the molecular mechanism underlying the virulence attenuation of rifampicin-resistant strain E9-302 and provided a new target for the subsequent study of the pathogenic mechanism of E. ictaluri.

• Clinical and Experimental Pediatrics
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• 제65권5호
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• pp.214-221
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• 2022

Diagnosing and treating latent tuberculosis infection (LTBI) is an important part of efforts to combat tuberculosis (TB). The Korean guidelines for TB published in 2020 recommend 2 LTBI regimens for children and adolescents: 9 months of daily isoniazid (9H) and 3 months of daily isoniazid plus rifampicin. Isoniazid for 6-12 months has been used to effectively treat LTBI in children for over 50 years. However, a long treatment period results in poor patient compliance. This review summarizes pediatric data on the treatment completion rate, safety, and efficacy of 4 months of daily rifampicin (4R) and evaluates the pharmacokinetics and pharmacodynamics of rifampicin in children. The 4R regimen has a higher treatment completion rate than the 9H regimen and equivalent safety in children. The efficacy of preventing TB is also consistent with that of 9H when summarizing reports published to date. A shorter treatment period could increase patient compliance and, therefore, prevent TB in more patients. By using an effective, safe, and highly compliant regimen for the treatment of children with LTBI, we would become one step closer to our goal of eradicating TB.