[COVID-19 impact on substance use and behaviors with addictive potential: Spanish Observatory on Drugs and Addictions survey.] / Impacto COVID-19 en el consumo de sustancias y comportamientos con potencial adictivo: encuesta del Observatorio Español de las Drogas y Adicciones.

The Covid-19 pandemic and the measures adopted for its control have had a significant impact, both in and at health, social and personal levels. The Spanish Observatory of Drugs and Addictions designed a survey to study the change in the pattern of consumption of psychoactive substances and other behaviors with addictive potential, such as the use of the Internet and gambling with money, in the Spanish population during the pandemic COVID-19. A random sample of 7,886 people aged 15 to 64 was interviewed by a telephone survey. The results show a decrease in the consumption of alcohol, tobacco and cannabis and non-internet gambling, along with an increase in the use of non-prescription hypnosedatives and the number of hours spent using the internet for recreational purposes, while online gambling remained unchanged. This overall decline in use occurs in a context of reduced access to illicit drugs, a consequence of the control measures adopted in the COVID-19 pandemic in Spain. The control measures also affected leisure environments, and this has possibly contributed to the changes observed, especially in heavy episodic alcohol consumption among young people, showing the impact of environmental prevention in tackling this problem.

La pandemia por Covid-19 y las medidas adoptadas para su control han supuesto un importante impacto, tanto sanitario como social y personal, a todos los niveles. El Observatorio Español de las Drogas y las Adicciones diseñó una encuesta para estudiar el cambio en el patrón de consumo de sustancias psicoactivas y otras conductas con potencial adictivo, como el uso de internet y el juego con dinero, en la población española durante la pandemia por Covid-19. Se realizó una encuesta telefónica sobre una muestra de 7.886 personas de 15 a 64 años representativa a nivel nacional. Los resultados muestran un descenso del consumo de alcohol, tabaco, cannabis y juego con dinero presencial, que contrasta con un aumento del consumo de hipnosedantes sin receta y del número de horas dedicado al uso de internet por diversión, mientras que el juego online permaneció sin cambios. El descenso generalizado de los consumos se ha producido en un contexto de diminución del acceso a las drogas ilegales, consecuencia de las medidas adoptadas para el control de la pandemia por COVID-19. Estas afectaron a los entornos de ocio lo que, posiblemente, ha contribuido a los cambios observados, en especial en los consumos intensivos de alcohol en jóvenes, sugiriendo la relevancia de las medidas de prevención ambiental en el abordaje de este problema.

Comparative therapeutic efficacy of a novel lyophilized amphotericin B lecithin-based oil-water microemulsion and deoxycholate-amphotericin B in immunocompetent and neutropenic mice infected with Candida albicans.

The in vivo efficacy of a new amphotericin B (AmB) oil-in-water lecithin-based microemulsion delivery system (M-AmB) compared to deoxycholate-AmB (D-AmB) was studied in an immunocompetent and neutropenic murine model of systemic candidiasis. D-AmB was administered at the maximum tolerated dose of 1 mg/kg whereas M-AmB was given at the doses of 1, 2 and 3 mg/kg; doses were well tolerated due to their reduced toxicity. Both formulations were administered 24, 48 and 72 h after infection in immunocompetent mice, and 2, 6 and 24 h after infection in neutropenic mice. Kaplan-Meier survival curves showed that the M-AmB treated group had a better survival time than infected mice without treatment used as a control group (P = 4.66 x 10(-6)), and the Mann-Whitney W statistical test indicated that it reduced the percentage of mortality and fungal load in the most representative organs. This new formulation is a designed competitor which has proved to present better results than D-AmB in an established infection not only in immunocompetent but in neutropenic mice as well.

Comparative pharmacokinetics and safety of a novel lyophilized amphotericin B lecithin-based oil-water microemulsion and amphotericin B deoxycholate in animal models.

Amphotericin B (AmB) has been a most effective systemic antifungal agent, but its use is circumscribed by the dose-limiting toxicity of the conventional micellar dispersion formulation Fungizone (D-AmB). To lower AmB-associated toxicity, AmB may be integrated into oil-in-water lecithin-based microemulsions. The present study compares the pharmacokinetic characteristics of D-AmB with the alternative formulation of AmB in microemulsion (M-AmB), which has proved effective in a murine candidiasis model. Both formulations were given by intravenous bolus: D-AmB 1 mg/kg, and M-AmB 0.5, 1 or 2 mg/kg. The pharmacokinetics of D-AmB and M-AmB have several differences, specifically with regard to the respective Cmax and AUC0- infinity values. Elimination of AmB from serum was biphasic for both M-AmB and D-AmB. Single-dose D-AmB (1 mg/kg) achieved a Cmax of 3.89 +/- 0.48 mg/L and an AUC0- infinity of 32.28 +/- 7.31 mg.h/L, whereas single-dose M-AmB (1 mg/kg) by comparison achieved a lower Cmax (2.92 +/- 0.54 mg/L) and a lower AUC0- infinity (21.89 +/- 5.17 mg.h/L). To evaluate the safety of M-AmB, a multiple-dose toxicity study was performed in groups of 10 mice, each receiving D-AmB 1 mg/kg, or M-AmB 1, 1.5, 2 or 3 mg/kg. The findings suggest that, in comparison with D-AmB, M-AmB produces no histologically demonstrable renal lesions, or changes in clinical chemistry.

Amphotericin B in oil-water lecithin-based microemulsions: formulation and toxicity evaluation.

A novel lecithin-based microemulsion containing AmB was developed to reduce the toxic effects of the drug, comparing it with the commercial formulation Fungizone. Phase diagrams containing the microemulsion region were constructed for pseudoternary systems composed of isopropil myristate (IPM)/Brij((R)) 96V/lecithin/water. The incorporation of AmB to the microemulsions was done following the Phase Inversion Temperature (PIT) method or by diluting the drug in the aqueous phase of the disperse system before forming the microemulsion. The percentage of drug entrapped in the microemulsion was analyzed by an HPLC method obtaining recoveries > 98%. Mean droplet size of the microemulsions chosen for the acute toxicity evaluation was of 45 nm, and the rheological studies showed that those microemulsions mentioned followed a Newtonian behavior. Different studies are described in this work to prove the stability of these new dosage forms. Acute toxicity results, determined by a graphic method, the probit binary model and the Reed and Muench method showed that lethal dose 50 (LD(50)) for AmB microemulsions was of 2.9 mgkg(-1) compared to 1.4 mgkg(-1) for the commercial deoxycholate suspension, Fungizone. The overall results indicate that treatment with AmB microemulsions was less toxic than Fungizone, suggesting a potential therapeutic application.