Repository logo

Browsing by Author "Morais, JA"

Now showing 1 - 6 of 6
  • Bioequivalence evaluation of three different oral formulations of ciprofloxacin in healthy volunteers
    Publication . Maya, MT; Goncalves, NJ; Silva, NE; Filipe, AE; Morais, JA
    Two bioequivalence studies were performed in twenty four healthy male volunteers with the objective of comparing the bioavailability of three different oral formulations of ciprofloxacin as immediate release tablets 250, 500 and 750 mg (test formulations) with a reference formulation at 500 and 750 mg strengths forms. In study 1, the subjects were enrolled in a single-dose, open-label, 3-period, crossover randomised study, designed to compare the bioavailability of two test formulations of ciprofloxacin (A and B) as 250 and 500 mg tablets, compared to the reference formulation (C), as 500 mg tablets. In study 2, the same 24-subjects were included in a single-dose, open-label, 2-period, crossover randomised study, designed to compare the bioavailability of one test formulation of ciprofloxacin (A) as compared to the reference formulation (B), both products as 750 mg tablets. In both studies multiple blood samples were collected over 24 hours post-dosing. One washout period of six days was observed between the periods. Plasma was harvested and assayed for ciprofloxacin using a selective and sensitive high-performance liquid chromatography (HPLC) method with UV detection. The pharmacokinetic parameter values of C-max and t(max) were obtained directly from plasma data, k(e) was estimated by log-linear regression, and AUC was calculated by trapezoidal rule. Different statistical tests were performed on the basis of untransformed and log-transformed data and the overall residual variance from ANOVA. Assuming the accepted tolerance intervals, a beta-error of 20 % and 90 % confidence intervals (alpha=0.10) of all the generally accepted tests (Westlake, Schuirmann test and Wilcoxon-Tukey nonparametric tests) showed that the formulations can be considered as bioequivalent with respect to the extent of absorption, given by the AUC(0-infinity) and with respect to rate of absorption as assessed by C-max and t(max).
    2003Journal article Metadata only Show more
  • Comparative Bioavailability of two immediate release tablets of enalapril/hydrochlorothiazide in healthy volunteers
    Publication . Maya, MT; Goncalves, NJ; Silva, NE; Filipe, AEP; Morais, JA; Caturla, MC; Rovira, M
    A bioequivalence study of two oral formulations of 20/12.5 mg tablets of enalaptil/hydrochlorothiazide was carried out in 20 healthy male volunteers according to a single dose, two-sequence, crossover randomized design. One washout period of nine days was observed between the two periods. Multiple samples were collected over 96 hours post-dosing. Bioavailability was evaluated on the basis of plasma concentrations of enalapril and its main active metabolite, enalaprilat and hydrochlorothiazide. Plasma samples were assayed for enalapril, enalaprilat and hydrochlorothiazide using a selective and sensitive high-performance liquid chromatography method with mass spectrometry detection (LC-MS). The pharmacokinetic parameter values of C-max and t(max) were obtained directly from plasma data, k(e) was estimated by log-linear regression, and AUC was calculated by trapezoidal rule. Different statistical tests were performed on the basis of untransformed and log-transformed data and the overall residual variance from ANOVA. Assuming the accepted tolerance intervals, a beta-error of 20% and 90% confidence intervals (alpha = 0.10), all the generally accepted tests (Schuirmann test and Wilcoxon-Tukey and Hauschke nonparametric tests) showed that the formulations can be considered as bioequivalent with respect to the extent of absorption, given by the AUC(0-infinity) and with respect to rate of absorption as assessed by C-max and t(max).
    2002Journal article Metadata only Show more
  • Determination of the antidepressant fluoxetine in human plasma by LC with UV detection
    Publication . Maya, MT; Domingos, CR; Guerreiro, MT; Morais, JA
    A selective and sensitive isocratic high-performance liquid chromatographic (HPLC) method was developed for the quantitative analysis of low concentrations of fluoxetine (FLX) in human plasma, with ultra-violet detection at 226 nm. A reversed-phase column, LiChrospher((R)) 60 RP-Select B (125 x 3 mm i.d., 5 mum) (Merck), was used to resolve FLX and diazepam (DZP) (internal standard) from endogenous matrix interferences. FLX was isolated from plasma by liquid-liquid extraction. Two identical HPLC systems were used, both validated under the same study conditions. Each chromatographic separation was completed in 30 min and the results showed a mean relative recovery of 101 and 99.3% and an overall precision (RSD%) of 4.78 and 6.09 for each HPLC system. The standard curve was linear for FLX concentrations over the range of 5.00-50.0 ng ml(-1) (R = 0.997 and 0.998).The limit of quantitation of FLX was 5 ng ml(-1) for both HPLC systems. The method described was applied to the analysis of plasma samples obtained from healthy subjects treated with one single oral dose of 40 mg of fluoxetine. (C) 2000 Elsevier Science B.V. All rights reserved.
    2000Journal article Metadata only Show more
  • Developments in the rat adjuvant arthritis model and its use in therapeutic evaluation of novel non-invasive treatment by SOD in Transfersomes
    Publication . Simoes, SI; Delgado, TC; Lopes, RM; Jesus, S; Ferreira, AA; Morais, JA; Cruz, MEM; Corvo, ML; Martins, MBF
    The aim of this study was firstly to refine a rat model of arthritis, the adjuvant arthritis (AA) model, by studying the time course of the disease, introducing new evaluation methods such as haematological and biochemical parameters in order to identify the main stages of the disease. An optimisation of treatment schedule and evaluation criteria was developed. This refinement provided novel non-invasive anti-inflammatory treatment of the AA with SOD by using mixed lipid vesicles specially developed for transdermal delivery, Transfersomes (M), this being the second major aim. The time course of AA includes a first stage: 1 day after the disease induction, the induced paw volume more than doubled and the paw circumference increased by approx. 50%. Two weeks later, another stage occurred where the disease shifted from the local arthritis form towards polyarthritis: an additional increase of volume and circumference of the induced and non-induced paws, occurred. The animals also started to loose weight around day 14 after the disease induction. Radiographic observable lesions increased correspondingly. Treatment of animals, started at day 1 after induction, by epicutaneous application of SOD-Tfs showed that I mg SOD/kg body weight is more efficient than 0.66 mg SOD /kg body weight. As a positive control, SOD liposomes intravenously injected were used for comparison and confirmed the biological efficiency of epicutaneously applied SOD in Tfs. SOD solution and empty Tfs epicutaneously applied exerted no effect. In addition, epicutaneous application of SOD-Tfs used prophylactically was able to suppress the induced rat paw oedema. Radiographic images showed less joint lesions in SOD-Tfs treated animals in comparison with control and placebo treated rats. It was shown for the first time that SOD incorporated into Tfs and applied onto a skin area not necessarily close to the inflamed tissue is able to promote non-invasive treatment of induced arthritis. (c) 2004 Elsevier B.V. All rights reserved.
    2005Journal article Metadata only Show more
  • Simple high-performance liquid chromatographic assay for the determination of ciprofloxacin in human plasma with ultraviolet detection
    Publication . Maya, MT; Goncalves, NJ; Silva, NB; Morais, JA
    A simple high-performance liquid chromatographic method is described for the quantitative analysis of ciprofloxacin in human plasma. Following protein precipitation from plasma by means of 6% perchloric acid, the upper layer which contains the analyte and the internal standard lomefloxacin, was analysed on a reverse phase column LiChrospher(R) 60 RP-select B (5 mum) (EcoCART(R) 125-3) with ultraviolet detection at 280 nm. The mobile phase was acetic acid 5%-methanol-acetonitrile (90:5:5, v/v/v). The assay was linear for ciprofloxacin over the concentration range of 0.050 to 6.00 mug ml(-1). The limit of quantification (LOQ) was 0.050 mug ml(-1). The method was successfully applied to a bioavailability study with five different ciprofloxacin formulations. (C) 2001 Elsevier Science B.V. All rights reserved.
    2001Journal article Unknown Show more
  • 2004Journal article Unknown Show more