Innovative prolonged-release oral alkalising formulation allowing sustained urine pH increase with twice daily administration: randomised trial in healthy adults.

A multi-particulate fixed-dose combination product, consisting of a combination of two alkalising salts formulated as prolonged-release granules, ADV7103, was developed to obtain a sustained and prolonged alkalising effect. The specific release of both types of granules was shown in vitro through their dissolution profiles, which indicated that potassium citrate was released within the first 2-3 h and potassium bicarbonate up to 10-12 h after administration. The long-lasting coverage of ADV7103 was confirmed through a randomised, placebo-controlled, double-blind, two-period study, measuring its effect on urine pH in healthy adults (n = 16) at doses of alkalising agent ranging between 0.98 and 2.88 meq/kg/day. A significant increase of urine pH with a positive dose-response in healthy adult subjects was shown. Urine pH above 7 was maintained during 24 h with a dosing equivalent to 1.44 meq/kg twice a day, while urine pH was below 6 most of the time with placebo. The effect observed was non-saturating within the range of doses evaluated and the formulation presented a good safety profile. ADV7103 provided an effective prolonged release of alkalising salts to cover a 12-h effect with adequate tolerability and could afford a twice a day (morning and evening) dosing in patients requiring long-term treatment.

In vivo high-frequency ultrasonic characterization of human dermis.

The aim of this study is in vivo skin tissue characterization of young and old human cutaneous tissues by estimating the slope of the attenuation coefficient. The method used is the centroid algorithm with a second-order autoregressive model to perform the spectral analysis. Backscattered signals are acquired with a 40-MHz transducer fixed on a three-dimensional robot. Diffraction phenomena are eliminated via an axial translation of the transducer that allows the acquisition of the signal in the focal zone. The slope of the attenuation coefficient is estimated on phantoms of known attenuation, in order to validate the method. Preliminary measurements of the slope of the attenuation coefficient are subsequently performed in the echographic mode on abdominal human skin samples in vitro at 40 MHz. After assessing the reproducibility of the measurement of the attenuation coefficient slope in human dermis at 40-MHz in vivo, this is carried out on the volar face of the forearm of 150 healthy subjects aged 14-85 yr. The values measured range from 0.7 to 3.6 dB/cm.MHz. The main result of this study is the decrease with advancing age of the attenuation coefficient slope, which may reflect structural modifications of human dermis with age.

High-frequency estimation of the ultrasonic attenuation coefficient slope obtained in human skin: simulation and in vivo results.

In vivo ultrasonic characterization of the skin was performed at 40 MHz by estimating the slope of the attenuation coefficient in the human dermis. The centroid algorithm was first tested on simulated backscattered RF lines with a second-order autoregressive model to carry out the spectral analysis. A relative error of less than 8.5% and a relative precision of less than 6% were predicted for a 2-mm tissue thickness and for temporal window sizes ranging from 0.25 to 0.45 micros. In vivo measurements performed on 138 healthy volunteers yielded values of the attenuation coefficient slope ranging from 0.8 to 3.6 dB/cm MHz. A decrease was observed with advancing age, but no significant difference appeared between men and women. The results from this study suggest that this acoustic parameter shows the effect of the ageing process on normal skin tissue in vivo.