Low-dose inhaled versus standard dose oral form of anti-tubercular drugs

Katiyar, Sandeep; Bihari, Shailesh; Prakash, Shivesh

doi:10.4103/0022-3859.41823

Cited by 23 publications

(2 citation statements)

References 2 publications

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“…This was a retrospective analysis of primary pharmacokinetic data from three original studies published by Conte et al, O'Brien et al, and Katiyar et al (17)(18)(19). Details about subjects' characteristics, informed consent, and study design are fully available in those publications (17)(18)(19). Briefly, the study by Conte et al (17) included 80 adult volunteers without TB, i.e., 20 men with AIDS, 20 men without AIDS, 20 women with AIDS, and 20 women without AIDS.…”

Section: Methodsmentioning

confidence: 99%

Population Modeling and Simulation Study of the Pharmacokinetics and Antituberculosis Pharmacodynamics of Isoniazid in Lungs

Lalande

Bourguignon

Bihari

et al. 2015

Antimicrob Agents Chemother

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Among first-line antituberculosis drugs, isoniazid (INH) displays the greatest early bactericidal activity (EBA) and is key to reducing contagiousness in treated patients. The pulmonary pharmacokinetics and pharmacodynamics of INH have not been fully characterized with modeling and simulation approaches. INH concentrations measured in plasma, epithelial lining fluid, and alveolar cells for 89 patients, including fast acetylators (FAs) and slow acetylators (SAs), were modeled by use of population pharmacokinetic modeling. Then the model was used to simulate the EBA of INH in lungs and to investigate the influences of INH dose, acetylator status, and M. tuberculosis MIC on this effect. A three-compartment model adequately described INH concentrations in plasma and lungs. With an MIC of 0.0625 mg/liter, simulations showed that the mean bactericidal effect of a standard 300-mg daily dose of INH was only 11% lower for FA subjects than for SA subjects and that dose increases had little influence on the effects in either FA or SA subjects. With an MIC value of 1 mg/liter, the mean bactericidal effect associated with a 300-mg daily dose of INH in SA subjects was 41% greater than that in FA subjects. With the same MIC, increasing the daily INH dose from 300 mg to 450 mg resulted in a 22% increase in FA subjects. These results suggest that patients infected with M. tuberculosis with low-level resistance, especially FA patients, may benefit from higher INH doses, while dose adjustment for acetylator status has no significant impact on the EBA in patients with low-MIC strains.

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Section: Methodsmentioning

confidence: 99%

Population Modeling and Simulation Study of the Pharmacokinetics and Antituberculosis Pharmacodynamics of Isoniazid in Lungs

Lalande

Bourguignon

Bihari

et al. 2015

Antimicrob Agents Chemother

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“…It is worth stressing that an increment of the Soluplus ® concentration from 3% w / v to 10% w / v was required for the co-encapsulation of both RIF and CUR. Then, the RIF concentration was 10 mg/mL since it is clinically relevant for a pulmonary dosage form taking into account that the RIF concentration in an inhalable formulation could be approximately 100-fold lower than in an oral dosage form [ 44 ].…”

Section: Resultsmentioning

confidence: 99%

Inhalable Mannosylated Rifampicin–Curcumin Co-Loaded Nanomicelles with Enhanced In Vitro Antimicrobial Efficacy for an Optimized Pulmonary Tuberculosis Therapy

et al. 2022

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Among respiratory infections, tuberculosis was the second deadliest infectious disease in 2020 behind COVID-19. Inhalable nanocarriers offer the possibility of actively targeting anti-tuberculosis drugs to the lungs, especially to alveolar macrophages (cellular reservoirs of the Mycobacterium tuberculosis). Our strategy was based on the development of a mannose-decorated micellar nanoformulation based in Soluplus® to co-encapsulate rifampicin and curcumin. The former is one of the most effective anti-tuberculosis first-line drugs, while curcumin has demonstrated potential anti-mycobacterial properties. Mannose-coated rifampicin (10 mg/mL)–curcumin (5 mg/mL)-loaded polymeric micelles (10% w/v) demonstrated excellent colloidal properties with micellar size ~108 ± 1 nm after freeze-drying, and they remain stable under dilution in simulated interstitial lung fluid. Drug-loaded polymeric micelles were suitable for drug delivery to the deep lung with lung accumulation, according to the in vitro nebulization studies and the in vivo biodistribution assays of radiolabeled (99mTc) polymeric micelles, respectively. Hence, the nanoformulation did not exhibit hemolytic potential. Interestingly, the addition of mannose significantly improved (5.2-fold) the microbicidal efficacy against Mycobacterium tuberculosis H37Rv of the drug-co-loaded systems in comparison with their counterpart mannose-free polymeric micelles. Thus, this novel inhaled nanoformulation has demonstrated its potential for active drug delivery in pulmonary tuberculosis therapy.

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