Evaluation of dosing regimen of respirable rifampicin biodegradable microspheres in the treatment of tuberculosis in the guinea pig

García-Contreras, Lucila; Sethuraman, Vasu V.; Kazantseva, M; Godfrey, Virginia; Hickey, Anthony

doi:10.1093/jac/dkl369

Cited by 48 publications

(30 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…and capreomycin particles (pulmonary), with no signs of adverse effects. Wet lung and spleen weights for treated animals were employed as an indication of the degree of inflammation of each organ (6,7,9,13,18,24). Figure 3 shows the organ weights corrected by body weight at the time of necropsy.…”

Section: Resultsmentioning

confidence: 99%

Inhaled Large Porous Particles of Capreomycin for Treatment of Tuberculosis in a Guinea Pig Model

García-Contreras

Fiegel

Telko

et al. 2007

Antimicrob Agents Chemother

Self Cite

131

View full text Add to dashboard Cite

Capreomycin is used for the treatment of multidrug-resistant tuberculosis (MDR-TB), but it is limited therapeutically by its severe side effects. The objectives of the present studies were (i) to design low-density porous capreomycin sulfate particles for efficient pulmonary delivery to improve local and systemic drug bioavailability and capacity to reduce the bacillary load in the lungs in a manner similar to that achieved with intramuscular injections; (ii) to determine pharmacokinetic parameters after pulmonary administration of these capreomycin particles; and (iii) to evaluate the efficacy of these particles in treating animals in a small-aerosol-inoculum guinea pig model of TB. Capreomycin particles were manufactured by spray drying and characterized in terms of size and drug content. Pharmacokinetic parameters were determined by noncompartmental methods with healthy guinea pigs after administration of capreomycin particles by insufflation. The efficacy of the particles was evaluated by histopathological analysis and in terms of wet organ weight and bacterial burden in TB-infected animals. Lungs of animals receiving a 14.5-mg/kg dose of capreomycin particles showed significantly lower wet weights and smaller bacterial burdens than those of animals receiving any other treatment. These results were supported by histopathological analysis. The feasibility of inhaling capreomycin in a novel powder form, with the ultimate objective of the treatment of MDR-TB, is demonstrated by pharmacokinetic and pharmacodynamic studies with guinea pigs. If applied to humans with MDR-TB, such a therapeutic approach might simplify drug delivery by eliminating injections and might reduce adverse effects through lowering the dose.Worldwide, there is an increase in multiple drug-resistant tuberculosis (MDR-TB), including reports of outbreaks of extensive MDR-TB in several countries (4, 36). Patients suffering from MDR-TB have infections which are resistant to at least two key drugs in the first-line regimen, namely, rifampin and isoniazid, in part as a consequence of poor compliance to the current first-line regimen (approximately 23% of active TB patients presently complete first-line treatment) (5). To treat MDR-TB, other, second-line antibiotics are needed and therapy lasts up to 2 years, typically requiring parenteral injection (2).Among the drugs injected is the polypeptide antibiotic capreomycin, the only second-line drug specifically indicated for MDR-TB. Capreomycin is a complex of four microbiologically active components that has been shown to be effective in combination with other appropriate anti-TB drugs in the treatment of pulmonary Mycobacterium tuberculosis infections when the primary agents (in particular isoniazid and rifampin) have become ineffective as a result of bacterial resistance or toxicity. The drug is painful to receive by injection and is associated with serious side effects, such as anorexia, thirst, anemia, and notably, nephrotoxicity and damage to the auditory and vestibular divisions of cranial nerv...

show abstract

Section: Resultsmentioning

confidence: 99%

Inhaled Large Porous Particles of Capreomycin for Treatment of Tuberculosis in a Guinea Pig Model

García-Contreras

Fiegel

Telko

et al. 2007

Antimicrob Agents Chemother

Self Cite

131

View full text Add to dashboard Cite

show abstract

“…One such treatment is a drug delivery system that sustains release of drugs and targets the primary site of action, the lungs. Rifampicin and other antitubercular drugs have been investigated in polymeric particle form for inhalation as both microparticles (34)(35)(36)(37) and nanoparticles (38)(39)(40)(41). These studies have shown that treatment with nebulized or insufflated particles containing antibiotics is effective in decreasing bacterial counts in infected animals with reduced doses.…”

Section: Discussionmentioning

confidence: 99%

Formulation and Pharmacokinetics of Self-Assembled Rifampicin Nanoparticle Systems for Pulmonary Delivery

Sung¹,

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Aerosols of rifampicin solutions and suspensions of biodegradable particles have been delivered by this chamber for the treatment of tuberculosis [110,98].…”

Section: Passive Inhalationmentioning

confidence: 99%

In vivo animal models for drug delivery across the lung mucosal barrier☆

Cryan

Sivadas

García-Contreras

2007

Advanced Drug Delivery Reviews

130

View full text Add to dashboard Cite

Evaluation of dosing regimen of respirable rifampicin biodegradable microspheres in the treatment of tuberculosis in the guinea pig

Cited by 48 publications

References 31 publications

Inhaled Large Porous Particles of Capreomycin for Treatment of Tuberculosis in a Guinea Pig Model

Inhaled Large Porous Particles of Capreomycin for Treatment of Tuberculosis in a Guinea Pig Model

Formulation and Pharmacokinetics of Self-Assembled Rifampicin Nanoparticle Systems for Pulmonary Delivery

In vivo animal models for drug delivery across the lung mucosal barrier☆

Contact Info

Product

Resources

About