Rapid and sensitive ultra‐high‐pressure liquid chromatography method for quantification of antichagasic benznidazole in plasma: application in a preclinical pharmacokinetic study

Davanço, Marcelo Gomes; Campos, Marcelo Lattarulo; Peccinini, Rosângela Gonçalves

doi:10.1002/bmc.3386

Cited by 8 publications

(8 citation statements)

References 28 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Workman et al reported a similar C max , 36 g/ml, in mice treated with 78 mg/kg of BNZ (12). In this study, the elimination half-life (t 1/2b ) of BNZ was 2.03 h, which is similar to the values reported by Davanço et al, Moreira da Silva et al, and Workman et al, which were 2.7, 1.6, and 1.6 h, respectively (12,16,18). These short half-lives indicate a high metabolism, which is responsible for low oral bioavailability.…”

Section: Discussionsupporting

confidence: 89%

“…However, Morilla et al observed a BNZ t 1/2b of 3.5 h after intravenous administration (14). This result was not expected, because the t 1/2b of an orally administered drug should be longer than that of an intravenously administered one due to the absorption phase (18).…”

Section: Discussionmentioning

confidence: 96%

“…However, several methods have been described for BNZ quantification in animal and human plasma, urine, and milk (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). To evaluate BNZ biodistribution, a bioanalytical method was developed to determine its quantification in mouse tissues, including spleen, brain, heart, colon, liver, lung, and kidney.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Pharmacokinetics and Tissue Distribution of Benznidazole after Oral Administration in Mice

Perin

Silva

Fonseca

et al. 2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Specific chemotherapy using benznidazole (BNZ) for Chagas disease during the chronic stage is controversial due to its limited efficacy and toxic effects. Although BNZ has been used to treat Chagas disease since the 1970s, few studies about the biodistribution of this drug exist. In this study, BNZ tissue biodistribution in a murine model and its pharmacokinetic profile in plasma were monitored. A bioanalytical high-performance liquid chromatography method with a UV detector (HPLC-UV) was developed and validated according to the European Medicines Agency for quantification of BNZ in organs and plasma samples prepared by liquidliquid extraction using ethyl acetate. The developed method was linear in the BNZ concentration, which ranged from 0.1 to 100.0 g/ml for plasma, spleen, brain, colon, heart, lung, and kidney and from 0.2 to 100.0 g/ml for liver. Validation assays demonstrated good stability for BNZ under all conditions evaluated. Pharmacokinetic parameters confirmed rapid, but low, absorption of BNZ after oral administration. Biodistribution assays demonstrated different maximum concentrations in organs and similar times to maximum concentration and mean residence times, with means of 40 min and 2.5 h, respectively. Therefore, the biodistribution of BNZ is extensive, reaching organs such as the heart and colon, which are the most relevant organs affected by Trypanosoma cruzi infection, and also the spleen, brain, liver, lungs, and kidneys. Simultaneous analyses of tissues and plasma indicated high BNZ metabolism in the liver. Our results suggest that low bioavailability, instead of inadequate biodistribution, could be responsible for therapeutic failure during the chronic phase of Chagas disease.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Pharmacokinetics and Tissue Distribution of Benznidazole after Oral Administration in Mice

Perin

Silva

Fonseca

et al. 2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…The linear concentration range was 0.15 to 20 g/ml. These chromatographic conditions were used in previous studies of BNZ pharmacokinetics in rats (23).…”

Section: Methodsmentioning

confidence: 99%

Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study

Davanço

Campos

Rosa

et al. 2016

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

c Benznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediaterelease tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentration in vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease.

show abstract

“…18 Chromatography has been particularly important for drug quantification because of its very high sensibility and selectivity, 17 which has allowed this technique to be employed in the quantification of drugs isolated or in biological medium, but also to analyze the incorporation of drugs in nanocarriers as well as in release and stability studies. To the best of our knowledge, however, chromatographic methods for quantification of BZN in lipid nanostructures have not been developed yet.…”

Section: Introductionmentioning

confidence: 99%

Validation of a Chromatographic Analytical Method for Quantification of Benznidazole Incorporated in Nanostructured Lipid Formulations

Almeida¹,

Marcial²,

Gouveia³

et al. 2016

Journal of the Brazilian Chemical Society

View full text Add to dashboard Cite

Benznidazole (BNZ) has been employed in the treatment of Chagas disease; however, its low water solubility is a drawback, which can be overcome by incorporating BZN within nanostructured systems. The aim of this work was to validate a chromatographic method for determination of BZN incorporated in nanoemulsions (NE) and nanostructured lipid carriers (NLC). The method was validated according to the International Conference on Harmonization guidelines. No interferences from the excipients of both systems on the BZN peak were observed. Linearity presented a correlation coefficient higher than 0.99 in the range of 5.0-30.0 µg mL -1 . Relative standard deviation values for intra-and inter-days precision were lower than 2% and mean recovery ranged from 93.6 to 105.7%. BZN-loaded nanocarriers exhibited physico-chemical characteristics acceptable for parenteral administration and the encapsulation efficiency was almost 100% for both systems. The method shows a good potential to be employed in the determination of BZN in lipid nanostructures.

show abstract

Rapid and sensitive ultra‐high‐pressure liquid chromatography method for quantification of antichagasic benznidazole in plasma: application in a preclinical pharmacokinetic study

Cited by 8 publications

References 28 publications

Pharmacokinetics and Tissue Distribution of Benznidazole after Oral Administration in Mice

Pharmacokinetics and Tissue Distribution of Benznidazole after Oral Administration in Mice

Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study

Validation of a Chromatographic Analytical Method for Quantification of Benznidazole Incorporated in Nanostructured Lipid Formulations

Contact Info

Product

Resources

About