Relationship between the effects of alfuzosin on rat urethral and blood pressures and its tissue concentrations.

This study was undertaken in order to establish the alpha1-antagonist effects of alfuzosin on phenylephrine-induced increases in urethral and arterial blood pressures at 1 and 6 hours post dosing (10 mg/kg, p.o.). At each time, plasma and prostatic concentrations of alfuzosin were measured and correlations between tissue concentrations and pharmacological effects were calculated. At one and six hours post dosing, alfuzosin markedly shifted the urethral and arterial dose response curve to phenylephrine. At one hour, prostatic concentration was 4.1 times greater than plasma concentration (363 ng/g vs 88 ng/ml) and at 6 hours this ratio reached 8.6 times (167 ng/g vs 20 ng/ml). By taking together the data points obtained at 1 and 6 hours we showed that the effects of alfuzosin on urethral pressure were correlated with prostate levels (r=0.906, p<0.01) and the effects on arterial blood pressure were correlated with plasma levels (r=0.941, p<0.01). These results suggest that a preferential distribution of alfuzosin in prostatic tissue may play a role in its functional uroselectivity.

Comparison of HPLC and RIA methods applied to the quantification of amisulpride in human plasma.

Quantification of amisulpride occurred up-till now using radioimmunoassay (RIA). A high performance liquid chromatographic (HPLC) assay with fluorimetric detection has been developed, which can be reproduced easily by any other laboratory. The aim of this paper is to compare amisulpride plasma levels (determined by RIA and HPLC) in 51 patients who received daily up to 800 mg of amisulpride in fractioned doses by IM or oral route, eventually together with other medications. Assay conditions and characteristics are briefly described and discussed. Results obtained with RIA and HPLC are compared and relative errors between both methods are calculated and examined as a function of the concentrations quantified. Correlation analysis using the concentrations (linear correlation) or their logarithm (logarithmic correlation) were realized for different concentration ranges. In fact, in the present case, logarithmic correlation was a more appropriate data processing method, which showed intercepts close to 0 and slopes close to 1. In conclusion, both methods are specific and sensitive enough to ensure the follow up of clinical studies. RIA may therefore be replaced whenever necessary by PHLC, without subsequent influence on the results.