Methotrexate (MTX), which presents high inter-individual variability, is part of the Brazilian Osteosarcoma Treatment Group (BOTG) protocol. This work aimed to develop a MTX population pharmacokinetic model (POPPK) for Brazilian children with osteosarcoma (OS) following the BOTG protocol to guide rescue therapy and avoid toxicity. The model was developed in NONMEM 7.
View Article and Find Full Text PDFUsing cycloalkyl and electron-donating groups to decrease the carbonyl electrophilicity, a novel series of 2-(quinoline-4-yloxy)acetamides was synthesized and evaluated as inhibitors of (Mtb) growth. Structure-activity relationship studies led to selective and potent antitubercular agents with minimum inhibitory concentrations in the submicromolar range against drug-sensitive and drug-resistant Mtb strains. An evaluation of the activity of the lead compounds against a spontaneous mutant strain indicated that the structures targeted the cytochrome complex.
View Article and Find Full Text PDFPharm Res
September 2022
Purpose: 5'-methoxynobiletin (5'-MeONB), a polymethoxyflavone isolated from A. conyzoides, has shown anti-inflammatory property. Nevertheless, the antinociceptive activity and pre-clinical pharmacokinetics (PK) characteristics of 5'-MeONB remain unknown.
View Article and Find Full Text PDFAntimalarial drugs have been suggested as promising scaffolds with anti-tubercular activities. In this work, we demonstrated, for the first time, the effectiveness of tafenoquine against mycobacteria. Firstly, tafenoquine inhibited the growth of Mycobacterium smegmatis and Mycobacterium tuberculosis with lower MICs values as compared to other antimalarial drugs, such as mefloquine, chloroquine, and primaquine.
View Article and Find Full Text PDFInt J Pharm
March 2021
The in vivo skin penetration by dermal microdialysis and the pharmacological efficacy of a chitosan hydrogel containing capsaicinoids-loaded nanocapsules (CHNC) was evaluated in this study. Such gel has previously been proven to control capsaicinoids release and decrease the drugs side effects in humans. The nanocapsules containing capsaicinoids had an average size around 150 nm, with a low polydispersity index, positive zeta potential, and high encapsulation efficiency of the drugs.
View Article and Find Full Text PDFJ Pharm Biomed Anal
September 2019
A bioanalytical LC-MS/MS method was developed and validated for the simultaneous quantification of capsaicin (CAPS) and dihydrocapsaicin (D-CAPS) in dermal microdialysis samples from rats. Capsaicinoids were separated by using a C18 column, with a mobile phase of water and acetonitrile, both with 0.1% of formic acid, eluted as a gradient.
View Article and Find Full Text PDFIQG-607 is an analog of isoniazid with anti-tuberculosis activity. This work describes the development and validation of an HPLC method to quantify pentacyano(isoniazid)ferrate(II) compound (IQG-607) and the pharmacokinetic studies of this compound in mice. The method showed linearity in the 0.
View Article and Find Full Text PDFThis work describes the development and validation of a quantitative and confirmatory method to determination of nine fluoroquinolones residues in poultry, bovine, swine and fish muscle using LC-MS/MS. Sample preparation was based in a fast solvent extraction with acetonitrile with 1% of formic acid followed by a low-temperature clean up procedure and centrifugation, without further steps. The recoveries ranged between 79% and 115%.
View Article and Find Full Text PDFA simple and fast quantitative and confirmatory multi-residue method was developed and validated for the determination of 14 coccidiostats residues in poultry muscle and eggs using liquid chromatography-tandem mass spectrometry (LC/MS-MS). The compounds were analyzed in a single run including lasalocid A, maduramicin, monensin, narasin, salinomycin, semduramicin, robenidine, diclazuril, toltrazuril, trimethoprim, clopidol, amprolium, diaveridine and nicarbazin (as the marker residue dinitrocarbanilide). A low-cost extraction and clean up procedure was optimized without the need of solid-phase extraction.
View Article and Find Full Text PDFBackground: The inhibition of pyrimidine biosynthesis by blocking the dihydroorotate dehydrogenase (DHODH) activity, the prime target of leflunomide (LEF), has been proven to be an effective strategy for rheumatoid arthritis (RA) treatment. However, a considerable proportion of RA patients are refractory to LEF. Here, we investigated lapachol (LAP), a natural naphthoquinone, as a potential DHODH inhibitor and addressed its immunosuppressive properties.
View Article and Find Full Text PDFThis work aimed to develop nanocapsules (NC) coated with polysorbate 80 (P80), cationic chitosan (CS) or polyethylene glycol (PEG) using clozapine (CZP) as the drug model. The zeta potential, pH and encapsulation efficiency were directly affected by the CS coating. Using the bag dialysis method, the in vitro CZP release from CS-coated nanocapsules was similar to the PEG-coated at pH 7.
View Article and Find Full Text PDFThe aim of this paper was to analyze the impact of anesthesia induced by urethane on pharmacokinetics (PK) parameters of fluconazole (FCZ), mostly eliminated via renal excretion and voriconazole (VRC), eliminated mainly by hepatic metabolism. FCZ and VRC PK were investigated after administration of 10 mg/kg i.v.
View Article and Find Full Text PDFA novel LC-MS/MS method was developed for the quantification of vildagliptin in an aqueous matrix. The method was successfully validated, meeting all the requisites of US Food and Drug Administration guide for a bioanalytical method. The developed method presented a limit of quantification of 10 ng/mL and the range of concentration achieved was 10-1875 ng/mL.
View Article and Find Full Text PDFThis report presents an exceptional case of uterine avulsion following a cold-knife conization, an unprecedented surgical complication of a common gynecological procedure. Furthermore, it describes the outcomes of the conservative laparoscopic reconstruction that was performed. A 30-year-old nulliparous was referred to our department with secondary amenorrhea and cyclic pelvic pain following a cold-knife conization performed 9 months previous in another institution.
View Article and Find Full Text PDFFood Addit Contam Part A Chem Anal Control Expo Risk Assess
July 2012
A reliable, simple and sensitive liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS) confirmation method has been developed for chloramphenicol (CAP) determination in honey, fish and prawns. For honey, samples were extracted with ethyl acetate, an aliquot was evaporated to dryness and re-dissolved in mobile phase. For fish and prawns, tissues were extracted with acetonitrile and chloroform.
View Article and Find Full Text PDFJ Chromatogr B Analyt Technol Biomed Life Sci
November 2011
A simple, accurate and precise high-performance liquid chromatographic method with fluorescence detection was developed and validated for the determination of gemifloxacin (GEM) in rat plasma using furosemide as internal standard (I.S.).
View Article and Find Full Text PDFBackground/aims: the determination of oral bioavailability of drugs which follow nonlinear pharmacokinetics is difficult and few methods are available. In this work, an alternative approach to determine oral bioavailability of voriconazole (VRC), used as a model drug, is presented.
Methods: VRC pharmacokinetics was investigated in Wistar rats after p.
Soft agglomerates containing pantoprazole-loaded microparticles were developed with the aim of prompt delivery of gastro-resistant particles. The objective was to evaluate the relative bioavailability in dogs after the oral administration of soft agglomerates. Gastro-resistant pantoprazole-loaded microparticles prepared by spray drying were mixed with mannitol/lecithin spray-dried powder and agglomerated by vibration.
View Article and Find Full Text PDFIn this work, previously published and unpublished results on biological activity of Hypericum caprifoliatum, a native species to South Brazil, are presented. Lipophilic extracts obtained from this species showed an antidepressant-like activity in mice and rat forced swimming test. Results from in vivo experiments suggest an effect on the dopaminergic transmission.
View Article and Find Full Text PDFThe aim of this work was to establish models and to differentiate the kinetic release behavior of drug models from nanocapsules, nanoemulsion and nanospheres by physico-chemical characterization and release experiments. SAXS analysis showed that the polymer is organized in the nanocapsules, while in the nanospheres the sorbitan monostearate is organized and acts as an impurity of the poly(epsilon-caprolactone) suggesting that constituents in these nanocarriers are differently organized. Formulations presented particle sizes ranging from 178 to 297 nm, probe content from 0.
View Article and Find Full Text PDFThis work investigated the pharmacokinetics of a new N-phenylpiperazine derivative (LASSBio-581), active on dopaminergic system. LASSBio-581 plasma concentrations were determined in rats after bolus administration of 10mg/kg, i.v.
View Article and Find Full Text PDFThalidomide has anti-angiogenic and immunomodulatory activity, exhibiting antitumour effects in patients with multiple myeloma and, more rarely, in several other solid tumours. We evaluated the single-agent antitumour activity and toxicity profile of thalidomide in patients with metastatic malignant melanoma, as well as its plasma pharmacokinetics and pharmacodynamic effects [vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) levels]. A two-stage Gehan method was used with a stopping rule after 14 consecutive non-responding patients.
View Article and Find Full Text PDFIntroduction: This study was designed to estimate the percentage of objective tumor responses, toxicity profile, and obtain additional information about the plasma pharmacokinetics of thalidomide in patients with refractory and progressing metastatic colorectal cancer.
Study Design: This phase II clinical trial was conducted according to the two-stage Simon method with the inclusion of consecutive patients. The study protocol was approved by the Institutional Review Board (IRB) of the Academic Hospital (HCPA) of the Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
Background: The purpose of this phase I study was to evaluate the toxicity profile, dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and plasma pharmacokinetics of oral etoposide, and to recommend a safe fractionated dose for phase II trials in pediatric patients with refractory solid tumors.
Material/methods: All patients had tumors no longer amenable to established forms of treatment. The initial dose of etoposide was 20 mg/m(2) TID for 14 days every 21 days (dose-level I).