Characterizing the mechanism of quetiapine distribution in lipid-core nanocapsules pseudo-phases using a validated LC/UV method

Quetiapine is an atypical antipsychotic used to treat schizophrenia. However, despite great interest for its chronic therapeutic use, quetiapine has some important side effects such as weight gain induction. The development of a quetiapine nanocarrier can potentially target the drug into central nervous system, resulting in a reduction of systemic side effects and improved patient treatment. In the present work, a simple liquid chromatography/ultraviolet detection (LC/UV) analytical method was developed and validated for quantification of total quetiapine content in lipid core nanocapsules as well as for determination of incorporation efficiency. An algorithm proposed by Oliveira et al. (2012) was applied to characterize the distribution of quetiapine in the pseudo-phases of the nanocarrier, leading to a better understanding of the quetiapine nanoparticles produced. The analytical methodology developed was specific, linear in the range of 0.5 to 100 µg mL−1 (r2 > 0,99), and accurate and precise (R.S.D < ±5%). The absolute recovery of quetiapine from the nanoparticles was approximately 98% with an incorporation efficiency of approximately 96%. The results indicated that quetiapine was present in a type III distribution according to the algorithm, and was mainly located in the core of the nanoparticle because of its logD in the formulation pH (6.86 ± 0.4)

Formulação enzimática de loção contendo queratinase microbiana como único agente de ação depilatória e promotora de absorção de fármacos

Universidade Federal do Rio Grande do SulCiências Básicas da SaúdeFarmáciaDepositad

Clinical and pharmacokinetic study of fractionated doses of oral etoposide in pediatric patients with advanced malignancies

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/m2 TID for 14 days every 21 days (dose-level I). Etoposide plasma pharmacokinetics were studied on day 1 of treatment and determined by HPLC. Results: Seventeen children were enrolled, 13 of whom were included in the pharmacokinetic study, for a total of 64 courses. Nine patients were included at dose-level I; grade 2–3 leucopenia was observed in 5. The dose was then raised to 25 mg/m2 (dose-level II) in another 8 patients; grade 3–4 leucopenia was observed in 4. This dose-level was therefore considered the MTD. The DLT was neutropenia. In patients at dose-level I and II the maximum plasma etoposide concentration was 2.97 and 8.59 μg/ml, respectively. Drug levels > 1 μg/ml were maintained for about 6.3 hours following drug administration at both dose-levels. Partial response was observed in 1 patient and 4 patients showed stable disease. Conclusions: Prolonged oral etoposide was well tolerated by our patients. Considering the MTD, and the fact that the patients included at dose-level I achieved an adequate (>1 μg/ml) plasma concentration of etoposide for a sufficient time, this dose level was recommended for phase II studies in pediatric malignancies. This work was performed at the Pediatric Oncology Service, Hospital de Clínicas de Porto Alegre; the Pediatric Hematology-Oncology Service, Hospital da Crianca Conceicao; and at the South American Office for Anticancer Drug Development (SOAD), Porto Alegre, Brazil

Fissuras lábio-palatinas : incidência e prevalência da patologia no Hospital de Clinicas de Porto Alegre : um estudo de 10 anos

As fissuras lábio-palatinas estão entre as anomalias congênitas mais comuns. Realizou-se um estudo no Hospital de Clínicas de Porto Alegre (HCPA) com o objetivo de avaliar a sua prevalência e analisar possíveis fatores predisponentes. Foram estudados todos os casos de Hssura lábio-palatiria nascidos no hospital no período de fevereiro de 1983 até julho de 1993. Foram utilizados dados do Estudo Colaborativo Latino-Americano de Malformações Congênitas (ECLAMC) e do Serviço do Arquivo Médico e Informação de Saúde (SAMIS) do H CP A. Ocorreram 41 casos de fendas lábiopalatinas em 31.058 nascimentos, correspondendo a uma prevalência de 1/757,5 nascimentos. Os casos foram descritos pelo método LAHSHAL, um novo sistema de documentação, que, por ser simples e facilmente memorizado, facilita a descrição clínica e seu uso em trabalhos de pesquisa.The cleft lip and palate is among the most frequent congenital anomalies. This study was done at the ''Hospital de Clínicas de Porto Alegre (HCPA)" aiming to evaluate possible risk factors involved in its genesis and its prevalance. All cases of cleft lip and palate, who were born at the hospital during the period of February,1983 until July, 1993, were accepted at the study. Data was provided by the ''Estudo Colaborativo Latino-Americano de Malformações Congênitas (ECLAMC)" and the "Serviço do Arquivo Médico e lnformação de Saúde (SAMJS)" at the HCPA. We found 41 cleft cases in 31.058 children born, corresponding to a prevalence of 1/757,5 deliveries. The cleft forms were described using the LAHSHAL method, a new description system that is simple and quickly memorized. It provides good clinical description and makes research easier

Análise farmacognóstica preliminar e atividade antiinflamatória das folhas de Sida carpiniflora (L. f.) K. Schum., Malvaceae :

Nas folhas de Sida carpinifolia (L. f.) K. Schum., Malvaceae, foi determinada a presença de rutinae quercetina por métodos cromatográficos e espectroscópicos. O extrato foi avaliado farmacologicamente, com vistas a sua atividade antiinflamatória.Flavonoids as rutin and quercetin were identifiedfrom theleaves of Sida carpinifolia (L.f) K.Schum., Malvaceae, know as "guanxuma preta" and widely spread in the south Brazil. The alcoholic extract has been pharmacologically evaluated concerning its antiinflamatory activity

Probability of target attainment of tobramycin treatment in acute and chronic pseudomonas aeruginosa lung infection based on preclinical population pharmacokinetic modeling

Abstract: Biofilms and infectious process may alter free antimicrobial concentrations at the site of infection. Tobramycin (TOB), an aminoglycoside used to treat lung infections caused by Pseudomonas aeruginosa, binds to alginate present in biofilm extracellular matrix increasing its minimum inhibitory concentration (MIC). This work aimed to investigate the impact of biofilm-forming P. aeruginosa infection on TOB lung and epithelial lining fluid (ELF) penetration, using microdialysis, and to develop a population pharmacokinetic (popPK) model to evaluate the probability of therapeutic target attainment of current dosing regimens employed in fibrocystic and non-fibrocystic patients. The popPK model developed has three compartments including the lung. The ELF concentrations were described by a penetration factor derived from the lung compartment. Infection was a covariate in lung volume (V3) and only chronic infection was a covariate in central volume (V1) and total clearance (CL). Simulations of the recommended treatments for acute and chronic infection achieved >90% probability of target attainment (PTA) in the lung with 4.5 mg/kg q24h and 11 mg/kg q24h, respectively, for the most prevalent P. aeruginosa MIC (0.5 mg/mL). The popPK model was successfully applied to evaluate the PTA of current TOB dosing regimens used in the clinic, indicating the need to investigate alternative posology