When the assumption of homoscedasticity is not met for analytical data, a simple and effective way to counteract the greater influence of the greater concentrations on the fitted regression line is to use weighted least squares linear regression (WLSLR). The purpose of the present paper is to stress the relevance of weighting schemes for linear regression analysis and to show how this approach can be useful in the bioanalytical field. The steps to be taken in the study of the linear calibration approach are described. The application of weighting schemes was shown by using a high-performance liquid chromatography method for the determination of lamotrigine in biological fluids as a practical example. By using the WLSLR, the accuracy of the analytical method was improved at the lower end of the calibration curve. Bioanalytical methods data analysis was improved by using the WLSLR procedure.

This was a double-blind, randomised, placebo-controlled study to investigate the pharmacokinetics and safety of trans-resveratrol. In four groups of ten healthy adult subjects (five males and five females), two subjects were randomized to receive placebo and eight subjects to receive trans-resveratrol 25, 50, 100 or 150 mg, six times/day, for thirteen doses. Peak plasma concentrations of trans-resveratrol were reached at 0.8-1.5 h postdose. Following the 13th dose of trans-resveratrol 25, 50, 100 and 150 mg, mean peak plasma concentration (C(max)) was 3.89, 7.39, 23.1 and 63.8 ng/mL and mean area under the plasma concentration-time curve (AUC(0-tau)) was 3.1, 11.2, 33.0 and 78.9 ng.h/mL. Interindividual variability was high, with coefficients of variation >40%. Trans-resveratrol half-life was 1-3 h following single-doses and 2-5 h following repeated dosing. Trough (C(min)) concentrations were < or = 1 ng/mL following 25 and 50 mg, 3 ng/mL following 100 mg and < 10 ng/mL following 150 mg. Trans-resveratrol pharmacokinetics showed circadian variation. Adverse events were mild in severity and similar between all groups. In conclusion, repeated administration was well-tolerated but produced relatively low plasma concentrations of trans-resveratrol, despite the high doses and short dosing interval used. Bioavailability was higher after morning administration.

No abstract

This systematic review was not funded. The authors declare that they have no conflicts of interest. Concept and study design were created by Pousinho, Morgado, and Alves. Pousinho took the lead in data collection, along with Alves, and data interpretation was performed by Pousinho, Falcão, and Alves. The manuscript was primarily written by Pousinho, along with Alves, and revised by Alves, Morgado, and Falcão.

Opicapone was well-tolerated and presented dose-proportional kinetics. Opicapone demonstrated marked and sustained inhibition of erythrocyte soluble COMT activity. Based on the observation that the half-life of COMT inhibition is independent of the dose and that it reflects an underlying kinetic process that is consistent with the k(off) value of the COMT-opicapone complex, we propose that the sustained COMT inhibition, far beyond the observable point of clearance of circulating drug, is due to the long residence time of the reversible complex formed between COMT and opicapone. Globally, these promising results provide a basis for further clinical development of opicapone.