[Thyroid effects of treatment with biotin]. / Efectos tiroideos del tratamiento con biotina.

TITLE: Efectos tiroideos del tratamiento con biotina.

A retrospective analysis of pharmacokinetic-pharmacodynamic parameters as indicators of the clinical efficacy of ceftizoxime.

OBJECTIVE: To analyse the relationship between a series of estimated pharmacokinetic-pharmacodynamic parameters and the reported efficacy of ceftizoxime. DESIGN: Retrospective literature search and analysis using different correlation models. METHODS: The following parameters were calculated for each group of patients included in the study from the simulated plasma concentration curves corresponding to the dosage regimen administered: (i) peak concentration at steady state divided by the minimum inhibitory concentration (CmaxSS/MIC); (ii) the time that the plasma drug concentration exceeded the MIC scaled to 24 hours at steady state [(tSS)24h > MIC]; (iii) the total area under the concentration-time curve over 24 hours at steady state divided by the MIC [(AUC(SS))24h/MIC]; and (iv) the AUC at steady state for the period of time that the concentration is above the MIC over a period of 24 hours divided by the MIC [(AUIC(SS))24h]. A univariate correlation analysis was performed considering efficacy [rate (%) of clinical cure or bacterial eradication] as the dependent variable and the pharmacokinetic-pharmacodynamic parameter as the independent variable, using linear and nonlinear models. RESULTS: (tSS)24h > MIC was the only parameter that was statistically correlated with efficacy, the linear model being the best choice among the 4 relationship approaches tested. A biased frequency distribution of reported efficacy data constricts the correlation analysis to a narrow range of efficacy and hinders interpretation of the results. CONCLUSIONS: The reporting of cases with low efficacy rates as well as those with high efficacy rates, including information on patient idiosyncrasies and the infecting organisms, would be of great help in performing retrospective analyses of the use of antimicrobial agents, leading to the optimisation of therapy with this type of drug in clinical practice.

A retrospective analysis of pharmacokinetic/pharmacodynamic indices as indicators of the clinical efficacy of ciprofloxacin.

A retrospective analysis of the relationship between estimated pharmacokinetic/pharmacodynamic indices and the reported efficacy of ciprofloxacin has been carried out using different correlation models. f1.gif" BORDER="0">, T(ss) > MIC, f2.gif" BORDER="0"> and AUIC(ss) were calculated for each clinical case included in the study, from simulated plasma level curves corresponding to the dosage regimen administered. A univariate correlation analysis was performed considering efficacy (%) as the dependent variable and indices as the independent variables according to linear and non-linear pharmacokinetic-pharmacodynamic models (PK-PD models). The results prove that log-transformation of the independent variable improves the data fitting to linear model. The four estimated indices show a log-linear relationship with outcome, T(ss) > MIC and AUIC(ss) being the parameters best correlated with percentage efficacy. The E(max) model with intrinsic response is an additional correlation strategy for T(ss) > MIC, leading to estimated values of E(max) and E(0) of 100.34 +/- 25.09% and 24.40 +/- 11.7%, respectively. The wide range of bacteria responsible for the infections considered, including Gram-positive pathogens such as staphylococci, might explain the good correlation between T(ss) > MIC and percentage efficacy found for ciprofloxacin in this study.

Basis of anti-infective therapy: pharmacokinetic-pharmacodynamic criteria and methodology for dual dosage individualisation.

Antimicrobial therapy should be designed on the basis of microbiological, as well as pharmacokinetic, criteria; microbiological parameters provide information about the susceptibility of the pathogen responsible for the infectious process while pharmacokinetic parameters give information about the potential ability of the drug in question to reach and remain at the sites of infection in the body. Microbiological parameters such as the minimum inhibitory concentration, minimum bactericidal concentration, bacterial titre, bactericidal rate and 'post-antibiotic effect' (PAE) must be considered. Among the pharmacokinetic parameters, the maximum serum concentration at steady state (CmaxSS), area under the concentration-time curve (AUC) and length of time that the serum concentrations exceed a particular value are the most useful in this context. Different relationships between these parameters, known as efficacy indices, have been established to predict the potential efficacy of antibacterial therapy. Antimicrobial dosage individualisation should be based on the optimisation of the efficacy index that best correlates with patient response. It seems appropriate to establish the degree of correlation among the different efficacy indices and clinical response observed in patients by means of a correlation analysis. This type of analysis can be either retrospective or prospective and may be based on linear or maximum response models. Simulation of the plasma concentration curves obtained with the particular regimen administered offers a methodology which is easy to apply and provides the pharmacokinetic information necessary to calculate the different efficacy indices. Information about the susceptibility of the pathogen to the antibacterial in question and about the response to the treatment used is also necessary for the correlation analysis. This type of analysis determines which of the indices is best correlated with efficacy and, hence, is the index to be optimised when attempting to individualise antibacterial therapy for different situations.

Effect of renal impairment on distribution of ofloxacin.

A study was made of the plasma and distribution kinetics of ofloxacin administered at a dosage of 400 mg orally to a group of healthy volunteers and a group of patients with renal impairment. Blood and blister fluid samples were taken at programmed times from all individuals included in the study. The analytical techniques for the determination of ofloxacin in both fluids were a plate diffusion method and a high-performance liquid chromatographic technique. The fitting of the experimental data to the kinetic model used was done with the help of the AUTOAN 2 and NONLIN 84 computer programs. In the groups of healthy volunteers, the elimination half-life mean values were found to be 5.1 and 5.9 h in plasma and blister fluid, respectively. The maximum concentration reached in plasma (3.9 micrograms/ml) proved to be slightly higher than that in interstitial tissue fluid (2.8 micrograms/ml). In the patients with renal impairment, the maximum concentrations in both plasma and blister fluid were significantly increased, in the order of 5 to 8 micrograms/ml in the former and 3 to 4 micrograms/ml in interstitial tissue fluid. The parameters seen to undergo an increase as a result of the renal impairment were the area under the curve of the plasma-time levels, the area under the curve of the blister fluid-time levels, and the elimination half-life in plasma and blister fluid. The degree of absorption and the access capacity of the drug to interstitial tissue fluid remained constant.