Sustained Release Characteristics of Rifampin-Loaded Microsphere Formulations in Nonhuman Primates

Quenelle, Debra C.; Winchester, Gary A.; Staas, Jay K.; Hoskins, Darrel E.; Barrow, Esther W.; Barrow, William W.

doi:10.1080/10717540490467366

Cited by 6 publications

(5 citation statements)

References 11 publications

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“…A number of papers examining HPLC methods for the determination of RIF concentrations have been published (6,11), but none have evaluated the stability of RIF in L-J medium and 7H9 broth. In our assay, a rapid, accurate, and reproducible HPLC method was developed and validated to measure rifampin concentrations in L-J medium and 7H9 broth medium.…”

Section: Discussionmentioning

confidence: 99%

Rifampin Stability in 7H9 Broth and Löwenstein-Jensen Medium

Jiang

et al. 2011

J Clin Microbiol

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The objectives of this study were to monitor the stability of rifampin (RIF) in Löwenstein-Jensen medium (L-J medium) and 7H9 broth, which are the media commonly used for drug susceptibility testing (DST) of Mycobacterium tuberculosis. Rifampin degradation in stock solution, 7H9 broth, and L-J medium and during the inspissation process for L-J medium preparation was serially monitored by high-performance liquid chromatography (HPLC). L-J medium-based DST was conducted to examine the effect of L-J medium storage on the DST outcome. The RIF stock solution was stable for at least 3 months when kept at either 4°C or ؊20°C; RIF in 7H9 broth and L-J medium was almost 50% decayed after 1 week of storage at 37°C, and rifampin could not be detected in 7H9 or L-J medium after 3 weeks or 6 weeks of storage at 37°C. Approximately half of the drug was decomposed after 4 months of storage at 4°C for both media, and after 6 months of storage at 4°C, RIF in L-J medium was undetectable, while 38% of RIF remained in 7H9 medium. Approximately 21, 24, 29, and 35% RIF degradations were detected when the L-J medium was coagulated at 75°C, 80°C, 85°C, and 90°C, respectively. The DST outcomes when using L-J medium stored for different periods of time were consistent with the RIF concentration monitoring data. Rifampin in stock solution is stable for at least 3 months at a reduced storage temperature. Media containing RIF should be prepared strictly according to validated standard operating procedures. RIF degradation is a possible reason for false resistance categorizations of M. tuberculosis isolates in the clinical laboratory.Although the global incidence of tuberculosis (TB) is declining, drug resistance is rapidly emerging and spreading (1, 13). Insufficient control measures have led to an increase in the prevalence of drug-resistant strains and, more importantly, the extent of drug resistance (10). In certain high-burden countries, the nature of multidrug-resistant (MDR) tuberculosis has evolved from incidental to epidemic.Drug susceptibility testing (DST) for mycobacteria based on drug-containing Löwenstein-Jensen (L-J) medium is a method used ubiquitously around the world, especially in resourcelimited settings, where it is usually the only laboratory technique for the diagnosis of drug-resistant TB. The proportion method and the absolute concentration method are widely used DST methods based on L-J medium. However, discordance between laboratory diagnosis and clinical treatment outcomes of drug-resistant tuberculosis is not uncommon (3, 9). Clinically, some patients with MDR TB diagnosed on the basis of DST achieve cure with first-line antituberculosis drug regimens. The cause for this inconsistency is worthy of investigation.Rifampin (RIF) is one of the most commonly used anti-TB drugs and is the backbone of most successful TB treatment regimens. In addition, more than 90% of RIF-resistant Mycobacterium tuberculosis strains are also resistant to isoniazid (INH); hence, RIF resistance is a marker for MDR TB (12).Clearly, an acc...

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Section: Discussionmentioning

confidence: 99%

Rifampin Stability in 7H9 Broth and Löwenstein-Jensen Medium

Jiang

et al. 2011

J Clin Microbiol

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“…This extends the therapeutic spectrum of this technology to another important mycobacterial pathogen important in the management of HIV-infected and other immunocompromized individuals. Compared with our achievements with rifampin-loaded microspheres, we were able to develop small rifabutin-loaded microspheres with drug content equivalent to the previous large formulation (23% wt/wt) and almost 4-fold above previous levels with the rifampin-loaded small formulation (5.8% wt/wt) (Quenelle et al 2001;Quenelle et al 2004).…”

Section: Discussionmentioning

confidence: 99%

“…This treatment results in elevated levels of rifampin in liver, lungs, and spleens 14-, 4-and 2-fold above MIC levels, respectively. Effects can be accomplished with only a single subcutaneous injection of the large formulation (2000 mg, 23% wt/wt) at day zero and/or 2 intravenous injections of the small formulation (2000 mg each, 5.8% wt/wt) at day 0 and day 7 (Quenelle et al 2004). …”

Section: Discussionmentioning

confidence: 99%

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Efficacy of Rifabutin-Loaded Microspheres for Treatment ofMycobacterium Avium-Infected Macrophages and Mice

Barrow

Quenelle

et al. 2007

Drug Delivery

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“…Controlled release rifampicin-loaded microspheres were evaluated in nonhuman primates (Quenelle et al, 2004). These microsheres were prepared by using biocompatible polymeric excipients of lactide and glycolide copolymers.…”

Section: Polymeric Microparticles For Tuberculosis Treatmentmentioning

confidence: 99%