Chromatographic analysis of antituberculosis drugs in biological samples

Holdiness, Mack R.

doi:10.1016/0378-4347(85)80201-2

Cited by 18 publications

(10 citation statements)

References 93 publications

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“…Compared to capreomycin, viomycin is not as well described in the literature as a treatment alternative for TB (6,16,20). Previous publications report that viomycin shares the major side effects of other aminoglycosides, such as nephro-and ototoxicity (20).…”

Section: Discussionmentioning

confidence: 99%

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Wild-Type MIC Distributions for Aminoglycoside and Cyclic Polypeptide Antibiotics Used for Treatment of Mycobacterium tuberculosis Infections

et al. 2010

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The aminoglycosides and cyclic polypeptides are essential drugs in the treatment of multidrug-resistant tuberculosis, underscoring the need for accurate and reproducible drug susceptibility testing (DST). The epidemiological cutoff value (ECOFF) separating wild-type susceptible strains from non-wild-type strains is an important but rarely used tool for indicating susceptibility breakpoints against Mycobacterium tuberculosis. In this study, we established wild-type MIC distributions on Middlebrook 7H10 medium for amikacin, kanamycin, streptomycin, capreomycin, and viomycin using 90 consecutive clinical isolates and 21 resistant strains. Overall, the MIC variation between and within runs did not exceed ؎1 MIC dilution step, and validation of MIC values in Bactec 960 MGIT demonstrated good agreement. Tentative ECOFFs defining the wild type were established for all investigated drugs, including amikacin and viomycin, which currently lack susceptibility breakpoints for 7H10. Five out of seven amikacin-and kanamycin-resistant isolates were classified as susceptible to capreomycin according to the current critical concentration (10 mg/liter) but were non-wild type according to the ECOFF (4 mg/liter), suggesting that the critical concentration may be too high. All amikacinand kanamycin-resistant isolates were clearly below the ECOFF for viomycin, and two of them were below the ECOFF for streptomycin, indicating that these two drugs may be considered for treatment of amikacinresistant strains. Pharmacodynamic indices (peak serum concentration [C max ]/MIC) were more favorable for amikacin and viomycin compared to kanamycin and capreomycin. In conclusion, our data emphasize the importance of establishing wild-type MIC distributions for improving the quality of drug susceptibility testing against Mycobacterium tuberculosis.

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Section: Discussionmentioning

confidence: 99%

“…The free fraction was calculated by multiplying the percentage of protein-free drug fraction with the C max , and the free fraction of this variable (fC max ) was divided by the corresponding MIC value (see Table 4 for the pharmacokinetic data used for calculations). All parameters were used in the lower range of published data (3,6,18,19).…”

Section: Strains Ofmentioning

confidence: 99%

Wild-Type MIC Distributions for Aminoglycoside and Cyclic Polypeptide Antibiotics Used for Treatment of Mycobacterium tuberculosis Infections

et al. 2010

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“…Peak detection for plasma was carried out on a liquid chromatography/mass spectrum/mass spectrum API III (Perkin-Elmer, Foster City, Calif.). The assay was designed specifically to detect ethionamide (9a); interfering peaks from ethionamide sulfoxide, the main metabolite, or other metabolites (15,17,18,22) were not observed. The following mass spectrometry conditions were used: (a) the multiple reaction monitor scanning mode was set at 167 to 139 for ethionamide and 244 to 215 for clemastine fumarate; (b) atmospheric pressure chemical positive ionization was used; (c) the sample inlet used a heated nebulizer at 450°C; (d) the discharge current was set to ϩ3 A; (e) the gas curtain flow rate was 1.2 liter/min (N 2 ϭ 99.999%); (f) the nebulizer pressure was 80 lb/in 2 ; and (g) the collision-activated dissociation gas mixture was 9.99% nitrogen-90.01% argon (set at 250 ϫ 10 12 molecules/cm 2 ).…”

Section: Methodsmentioning

confidence: 99%

Effects of AIDS and Gender on Steady-State Plasma and Intrapulmonary Ethionamide Concentrations

Conte

Golden²,

McQuitty

et al. 2000

Antimicrob Agents Chemother

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Ethionamide, 250 mg every 12 h for a total of nine doses, was administered to 40 adult volunteers (10 men with AIDS, 10 healthy men, 10 women with AIDS, and 10 healthy women). Blood was obtained for drug assay prior to administration of the first dose, 2 h after the last dose, and at the completion of standardized bronchoscopy and bronchoalveolar lavage, which were performed 4 h after the last dose. Ethionamide was measured in epithelial lining fluid (ELF) and alveolar cells (AC) using a new mass spectrometric method. The presence of AIDS or gender was without significant effect on the concentrations of ethionamide in plasma, AC, or ELF. Plasma concentrations (mean ؎ standard deviation [SD]) were 0.97 ؎ 0.65 and 0.65 ؎ 0.35 g/ml at 2 and 4 h after the last dose, respectively, and both values were significantly greater than the concentration of ethionamide in AC (0.38 ؎ 0.47 g/ml) (P < 0.05). The concentration of ethionamide was significantly greater in ELF (5.63 ؎ 3.8 g/ml) than in AC or plasma at 2 and 4 h and was approximately 10 to 20 times the reported MIC for ethionamide-susceptible strains of Mycobacterium tuberculosis. For all 40 subjects, the ELF/plasma concentration ratios (mean ؎ SD) at 2 and 4 h were 8.7 ؎ 11.7 and 9.7 ؎ 5.6, respectively. We conclude that the absorption of orally administered ethionamide, as measured in this study, was not affected by gender or the presence of AIDS. Ethionamide concentrations were significantly greater in ELF than in plasma or AC, suggesting that substantial antimycobacterial activity resides in this compartment.Ethionamide is a second-line, orally administered drug that is used for the treatment of tuberculosis. It is often combined with other antituberculous agents for the treatment of multiple-drug-resistant organisms. The usual dose is 250 to 500 mg two to four times per day (1, 21). The daily dose is limited by gastrointestinal toxicity. The elimination half-life in humans is approximately 2 to 3 h (18,19,22). Peak plasma concentrations occur at approximately 2 h postdosing and have been reported to be between 0.6 and 1.9 g/ml following an oral dose of 250 mg (11, 18) and 2.2 g/ml following an oral dose of 500 mg Ethionamide is active against tubercle bacilli that are growing within human macrophages (24). The in vivo penetration of ethionamide into pulmonary macrophages and epithelial lining fluid (ELF) in humans has not been reported. We (7-9) and others (2-4) have developed techniques for the measurement, in vivo, of the concentration of drugs in pulmonary ELF and alveolar cells (AC). The purpose of this study was to compare the steady-state plasma and intrapulmonary ethionamide concentrations in healthy volunteers and men and women with AIDS. MATERIALS AND METHODSStudy design and subjects. The investigation was prospective and nonblinded. After giving informed consent, subjects underwent a medical history, physical examination, purified protein derivative skin test, and baseline laboratory testing including complete blood count, platelet count, blood urea ni...

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“…The pharmacology of the most important antituberculosis drugs and their deter mination in biological fluids have been reviewed by Weber and Hein [40], Kenny and Strates [41], Holdiness [42,43]and Jenner [44].The importance of using specific methods for the determination of drugs in pharmacokinetic studies must be stressed since in the past recommendations concerning the treatment of patients with renal impairment have some times been made as a result of unreliable findings generated by studies using non-specific assays. The studies described in this review have therefore been restricted to those em ploying analytical methods which are believed to measure only the antimicrobially active unmetabolized drugs.…”

Section: Pharmacology Of the Antituberculosis Drugs And Recommendatiomentioning

confidence: 99%

Chemotherapy of Tuberculosis for Patients with Renal Impairment

Ellard¹

1993

Nephron

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Chromatographic analysis of antituberculosis drugs in biological samples

Cited by 18 publications

References 93 publications

Wild-Type MIC Distributions for Aminoglycoside and Cyclic Polypeptide Antibiotics Used for Treatment of Mycobacterium tuberculosis Infections

Wild-Type MIC Distributions for Aminoglycoside and Cyclic Polypeptide Antibiotics Used for Treatment of Mycobacterium tuberculosis Infections

Effects of AIDS and Gender on Steady-State Plasma and Intrapulmonary Ethionamide Concentrations

Chemotherapy of Tuberculosis for Patients with Renal Impairment

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