Absolute/Relative Bioavailability and Metabolism of Dodeca-2E,4E,8Z,10E/Z-Tetraenoic Acid Isobutylamides (Tetraenes) after Intravenous and Oral Single Doses to Rats

Abstract The relative bioavailability of trace minerals may vary between the sources and impact the animal performance. The study was carried out to evaluate the effect of TM source (Cu and Zn) on the liver concentration and performance of Nellore cattle supplemented in the growing phase during the transition between dry to rainy season. A hundred and twenty Nellore young bulls (BW = 349.72 ± 24 kg; 24 months), blocked by BW, were assigned randomly to twelve paddocks (six paddocks/treatment and 10 animals/paddock). Animals grazing Urochloa brizantha cv. Marandu and supplemented at 5 g/kg BW with soybean meal, corn and mineral mix (250 g/kg of CP and 650 g/kg de NDT, natural matter basis). Supplements consisted of 40 mg Cu and 148 mg Zn/kg DM from either inorganic TM (ITM) or hydroxy TM (HTM) Intellibond® sources. Liver samples were collected at the beginning and end of the study (three animals per paddock). Animals were weighed at each period (30 days) during three periods. Period was used as a REPEATED measurement for BW and values of initial BW as independent covariates for all variables. Paddock was considered experimental unit. Data were analyzed by ANOVA using PROC MIXED, SAS 9.4. The animals supplemented with HTM had higher (+0.037 kg/day) general ADG (day 0 to 90; P = 0.012), with 0.469 and 0.506 kg/day to ITM and HTM, respectively. Final BW (day 90) from animals fed HTM was 5.13 kg higher than ITM (391.97 vs. 397.11 kg BW; P = 0.030). No differences were found in the liver concentrations of Cu and Zn between ITM or HTM (P ≥ 0.288). Cu and Zn from HTM improve the performance of animals supplemented in pasture compared to ITM sources.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02506-15 ◽

2016 ◽

Vol 60 (4) ◽

pp. 2492-2498 ◽

Cited By ~ 8

Author(s):

Marcelo Gomes Davanço ◽

Michel Leandro Campos ◽

Talita Atanazio Rosa ◽

Elias Carvalho Padilha ◽

Alejandro Henao Alzate ◽

...

Keyword(s):

Chagas Disease ◽

Extended Release ◽

Hydroxypropyl Methylcellulose ◽

Immediate Release ◽

Relative Bioavailability ◽

Pharmacokinetic Parameters ◽

Therapeutic Success ◽

Preclinical Pharmacokinetics ◽

Bioavailability Study

ABSTRACTBenznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release 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 concentrationin 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.

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