High-performance liquid–chromatographic determination of rifampicin in plasma and tissues

Calleja, Ignacio; Blanco-Prieto, María José; Ruz, Noelia; Renedo, M. J.; Dios-Viéitez, María del Carmen

doi:10.1016/j.chroma.2003.12.041

Cited by 53 publications

(33 citation statements)

References 22 publications

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“…Butylated hydroxytoluene dissolved in acetonitrile was first added to the samples to achieve a final concentration of 0.1%, wt/vol, in order to minimize drug degradation (6). A solvent system comprising equal parts of dichloromethane and n-pentane was added to the samples (0.5 ml and 1 ml for the cell lysate and serum and tissue homogenates, respectively).…”

Section: Microparticles Containingmentioning

confidence: 99%

Intracellular Time Course, Pharmacokinetics, and Biodistribution of Isoniazid and Rifabutin following Pulmonary Delivery of Inhalable Microparticles to Mice

Verma

Kaur

Kumar

et al. 2008

Antimicrob Agents Chemother

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Intracellular concentrations of isoniazid and rifabutin resulting from administration of inhalable microparticles of these drugs to phorbol-differentiated THP-1 cells and the pharmacokinetics and biodistribution of these drugs upon inhalation of microparticles or intravenous administration of free drugs to mice were investigated. In cultured cells, both microparticles and dissolved drugs established peak concentrations of isoniazid (ϳ1.4 and 1.1 g/10 6 cells) and rifabutin (ϳ2 g/ml and ϳ1.4 g/10 6 cells) within 10 min. Microparticles maintained the intracellular concentration of isoniazid for 24 h and rifabutin for 96 h, whereas dissolved drugs did not. The following pharmacokinetic parameters were calculated using WinNonlin from samples obtained after inhalation using an in-house apparatus (figures in parentheses refer to parameters obtained after intravenous administration of an equivalent amount, i.e., 100 g of either drug, to parallel groups): isoniazid, serum half-life (t 1/2 ) ‫؍‬ 18. 63 h ؊1 ), and CL ‫؍‬ 11.68 ؎ 7.00 ml ⅐ h ؊1 (1.03 ؎ 0.11 ml ⅐ h ؊1 ). Drug targeting to the lungs in general and alveolar macrophages in particular was observed. It was concluded that inhaled microparticles can reduce dose frequency and improve the pharmacologic index of the drug combination.Several species of the genus Mycobacterium have evolved to survive in lung macrophages of the mammalian host, leading to granulomatous or latent tuberculosis (TB) (27). Chemotherapeutic regimens for TB require prolonged administration of multiple drugs through the oral route, but their ability to provide a lasting cure has not yet been established (7). We (18,21,29,30,38; H. Sen, J. Suryakumar, R. Sinha, R. Sharma, and P. Muttil, 3 September 2003, PCT patent application PCT/ IB2003/004694) and others (19, 23-26, 39, 40) have investigated several aspects of respirable or inhalable microparticles for treatment of pulmonary TB, first proposed by Hickey et al. (22,33,34). Particles developed by our group contain equal amounts of isoniazid and rifabutin and are meant for "adjunct therapy" of pulmonary TB through uptake by alveolar macrophages harboring Mycobacterium tuberculosis and/or related species. It is also speculated that, following uptake of microparticles, uninfected macrophages could traffic to lung areas where infected cells congregate. It has been demonstrated in animal experiments that inhaled microparticles target the drug payload to alveolar macrophages (21, 30) and enhance the efficacy of the incorporated agents (33, 34; Sen et al., PCT patent application PCT/IB2003/004694).The biopharmaceutics of both isoniazid (15,35,36) and rifabutin (3,4,31,32), both in humans and mice, are well known, and good correlations between the two species in terms of both kinetic data and therapeutic outcome have been observed (1).This report addresses the single-dose pharmacokinetics of isoniazid and rifabutin in polylactide microparticles administered by dry-powder inhalation to mice. Khuller et al. have extensively investigated the steady-s...

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Section: Microparticles Containingmentioning

confidence: 99%

Intracellular Time Course, Pharmacokinetics, and Biodistribution of Isoniazid and Rifabutin following Pulmonary Delivery of Inhalable Microparticles to Mice

Verma

Kaur

Kumar

et al. 2008

Antimicrob Agents Chemother

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“…This is somewhat surprising for an approved and frequently used clinical antibiotic, but rifampin is recognized as having potential therapeutic ratio issues in some situations. 23 Conversely, although useful for final drug testing, the safety ratio may be overly conservative, especially for early antimicrobial development. If this criterion were to be strictly applied, then it could have caused successful agents such as rifampin to be dropped from further consideration before they are fully evaluated.…”

Section: Efficacy and Toxicology Screening Approachmentioning

confidence: 99%

Early Stage Efficacy and Toxicology Screening for Antibiotics and Enzyme Inhibitors

et al. 2012

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The rise in organisms resistant to existing drugs has added urgency to the search for new antimicrobial agents. Aspartate β-semialdehyde dehydrogenase (ASADH) catalyzes a critical step in an essential microbial pathway that is absent in mammals. Our laboratory is using fragment library screening to identify efficient and selective ASADH inhibitors. These preliminary agents are then tested to identify compounds with desired antimicrobial properties for further refinement. Toward this end, we have established a microplate-based, dual-assay approach using a single reagent to evaluate antibiotic activity and mammalian cell toxicity during early stage development. The bacterial assay uses nonpathogenic bacteria to allow efficacy testing without a dedicated microbial laboratory. Toxicity assays are performed with a panel of mammalian cells derived from representative susceptible tissues. These assays can be adapted to target other microbial systems, such as fungi and biofilms, and additional mammalian cell lines can be added as needed. Application of this screening approach to antibiotic standards demonstrates the ability of these assays to identify bacterial selectivity and potential toxicity issues. Tests with selected agents from the ASADH inhibitor fragment library show some compounds with antibiotic activity, but as expected, most of these early agents display higher than desired mammalian cell toxicity. Keywordsantibiotic drug development, mammalian cell toxicity, cell-based assays, in vitro therapeutic ratio

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“…RIF is a very active antituberculosis drug that accelerates the metabolism of protease inhibitors. 3,4) Due to the increasing necessity to monitor plasma concentrations in HIV patients with tuberculosis, different methods such as spectroscopy, 5-9) fluorometry, [10][11][12] gas chromatography, 13) polarography, 14) amperometry 15) and high performance liquid chromatography [16][17][18][19][20][21] have been developed to measure RIF alone or in the presence of INH. These methods are expensive and need more expertise in experimentation in comparison with spectrophotometry.…”

Section: Rifampicin 3-[[4-methyl-1-piperazinyl)-imino]-methyl]-rifammentioning

confidence: 99%

“…gas chromatography, 13) polarography, 14) amperometry 15) and high performance liquid chromatography [16][17][18][19][20][21] have been developed to measure RIF alone or in the presence of INH. These methods are expensive and need more expertise in experimentation in comparison with spectrophotometry.…”

mentioning

confidence: 99%

Spectrophotometric Determination of Rifampicin through Chelate Formation and Charge Transfer Complexation in Pharmaceutical Preparation and Biological Fluids

Sadeghi

Karimi

2006

Chem. Pharm. Bull.

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Rifampicin, 3-[[4-methyl-1-piperazinyl)-imino]-methyl]-rifamycin SV, (RIF) (Fig. 1a) is a semi-synthetic derivative of Rifamycin SV.1,2) It can be used alone or in combination with other drugs, such as isoniazid (INH) and pyrazinamide, in treatment of tuberculosis, leprosy and other infectious diseases specially those resulting from AIDS. The high occurrence of tuberculosis in HIV infected subjects makes the management of HIV treatment complex. RIF is a very active antituberculosis drug that accelerates the metabolism of protease inhibitors. 3,4) Due to the increasing necessity to monitor plasma concentrations in HIV patients with tuberculosis, different methods such as spectroscopy, 5-9) fluorometry, [10][11][12] gas chromatography, 13) polarography, 14) amperometry 15) and high performance liquid chromatography [16][17][18][19][20][21] have been developed to measure RIF alone or in the presence of INH. These methods are expensive and need more expertise in experimentation in comparison with spectrophotometry.Spectrohotometric techniques continue to be the most preferred method for routine analytical work due to their simplicity and reasonable sensitivity with significant economical advantages. On the other hand, it is well known that p-benzoquinones such as 7,7,7,8-tetracyanoquinodimethane (TCNQ), 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and 2,3,5,6-Tetrachloro-1,4-benzoquinone (p-chloranil) as pelectron acceptors (Fig. 1b) often form highly colored electron-donor-acceptor (EDA) or charge transfer (CT) complexes with various donors which provides the possibility of determination of drugs by spectrophotometric methods.In order to develop a new method for determination of RIF in pure and pharmaceutical forms as well as characterize the behavior of RIF in EDA chemistry, we investigated spectrophotometrically the reactions of RIF with organic p-acceptors DDQ, TCNQ and p-chloranil. The absence of an extraction step in these assays and the efficiency of the method offer the ease and rapidity desired for measurement of RIF. Also, an extractive-spectrophotometric method based on the reaction of RIF with iron(III) was developed. The results were compared with other similar methods. The reaction pathways were investigated by IR and 1 H-NMR spectra. Results and DiscussionRIF was found to yield intense colors with p-acceptors in acetonitrile solution, most probably due to the CT complexation of RIF as n-electron donor with DDQ, TCNQ and pchloranil as p-electron acceptors. Figure 2 shows the absorption spectra of RIF, DDQ, TCNQ and p-chloranil and their complexes in acetonitrile. Acetonitrile was found to be an ideal solvent for the formation of charge transfer (CT) complex. Methanol, dichloromethane, chloroform and mixtures of methanol-acetonitrile were examined and produced lower absorbance reading. Acetonitrile was chosen as the best solvent due to intensely colored CT complex with high molar absorptivity values and more reproducibility of the measure- Two simple and accurate spectrophotometric methods for deter...

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High-performance liquid–chromatographic determination of rifampicin in plasma and tissues

Cited by 53 publications

References 22 publications

Intracellular Time Course, Pharmacokinetics, and Biodistribution of Isoniazid and Rifabutin following Pulmonary Delivery of Inhalable Microparticles to Mice

Intracellular Time Course, Pharmacokinetics, and Biodistribution of Isoniazid and Rifabutin following Pulmonary Delivery of Inhalable Microparticles to Mice

Early Stage Efficacy and Toxicology Screening for Antibiotics and Enzyme Inhibitors

Spectrophotometric Determination of Rifampicin through Chelate Formation and Charge Transfer Complexation in Pharmaceutical Preparation and Biological Fluids

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