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.
Developed originally as an antimalarial agent, hydroxychloroquine sulfate (HCQS) is often used as a slow-acting drug in treating disorders of connective tissue. Over the past two decades, several data have been accumulated on the systemic effects of HCQS, expanding the potential uses of this drug in different therapeutic classes. The purpose of this article was to conduct a narrative review with qualitative approach on clinical, pharmacokinetic and technological aspects of HCQS, aiming to gather relevant pieces of information for the development of new therapeutic approaches to this drug. A search of the literature of scientific experimental and theoretical studies in the period 1980-2013 was performed. According to the data collected, among the activities HCQS, there are the indications for the treatment of autoimmune diseases such as lupus erythematosus and rheumatoid arthritis. Reports also indicate that HCQS improves insulin sensitivity, ability to reduce thromboembolic events, reduction of lipid levels and treatment for infection by human immunodeficiency virus. The evidence found out ocular and cutaneous adverse effects and the formation of three chiral active metabolites, what encourages studies to evaluate the kinetic behavior of HCQS and the intrinsic physicochemical characteristics of the drug, which is yet poorly described in the literature.
The present study was performed to compare the bioavailability of 2 risedronate sodium 35 mg film-coated tablet formulations (test formulation and reference formulation). Prior to the present study, in vitro comparative dissolution test has been conducted for test and reference formulations. Dissolution profiles shown that more than 85% of the drug is dissolved within 15 min at pH 1.2, pH 4.5, and pH 6.8.This study was a randomized, single-blind, 2-period, 2-sequence cross-over study which included 48 evaluable healthy adult male and female subjects under fasting condition. In each of the 2 study periods (separated by a washout of 3 weeks) a single dose of test or reference drug was administered. The pharmacokinetic parameters assessed in this study were cumulative urinary excretion from drug administration to 72 h (Ae72h) and maximum urine excretion rate (dAe/dtmax). These parameters were determined from urine concentrations of risedronate and urine volume. Urinary concentrations of the drug were determined by high performance liquid chromatographic method with UV detector.The geometric mean ratios (90% CI) of the test drug/reference drug for risedronate were 106.60% (92.34-123.07%) for Ae72h and 104.75% (88.86-123.47%) for dA/dtmax. The geometric mean ratios calculated for Ae72h and dA/dtmax of risedronate were within the bioequivalence range (80.00-125.00% for Ae72h and dA/dtmax). It was concluded that the 2 risedronate sodium film-coated tablets (test and reference drugs) were bioequivalent.
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