ABSTRACT
The pharmacokinetics of scorpion venom and its toxins has been investigated in experimental models using adult animals, although, severe scorpion accidents are associated more frequently with children. We compared the effect of age on the pharmacokinetics of tityustoxin, one of the most active principles of Tityus serrulatus venom, in young male/female rats (21-22 days old, N = 5-8) and in adult male rats (150-160 days old, N = 5-8). Tityustoxin (6 µg) labeled with 99mTechnetium was administered subcutaneously to young and adult rats. The plasma concentration vs time data were subjected to non-compartmental pharmacokinetic analysis to obtain estimates of various pharmacokinetic parameters such as total body clearance (CL/F), distribution volume (Vd/F), area under the curve (AUC), and mean residence time. The data were analyzed with and without considering body weight. The data without correction for body weight showed a higher Cmax (62.30 ± 7.07 vs 12.71 ± 2.11 ng/ml, P < 0.05) and AUC (296.49 ± 21.09 vs 55.96 ± 5.41 ng h-1 ml-1, P < 0.05) and lower Tmax (0.64 ± 0.19 vs 2.44 ± 0.49 h, P < 0.05) in young rats. Furthermore, Vd/F (0.15 vs 0.42 l/kg) and CL/F (0.02 ± 0.001 vs 0.11 ± 0.01 l h-1 kg-1, P < 0.05) were lower in young rats. However, when the data were reanalyzed taking body weight into consideration, the Cmax (40.43 ± 3.25 vs 78.21 ± 11.23 ng kg-1 ml-1, P < 0.05) and AUC (182.27 ± 11.74 vs 344.62 ± 32.11 ng h-1 ml-1, P < 0.05) were lower in young rats. The clearance (0.03 ± 0.002 vs 0.02 ± 0.002 l h-1 kg-1, P < 0.05) and Vd/F (0.210 vs 0.067 l/kg) were higher in young rats. The raw data (not adjusted for body weight) strongly suggest that age plays a pivotal role in the disposition of tityustoxin. Furthermore, our results also indicate that the differences in the severity of symptoms observed in children and adults after scorpion envenomation can be explained in part by differences in the pharmacokinetics of the toxin.
Subject(s)
Animals , Male , Rats , Scorpion Venoms , Scorpions , Age Factors , Area Under Curve , Body Weight , Injections, Subcutaneous , Rats, Sprague-DawleyABSTRACT
Foram colhidas amostras de sangue de 30 pacientes com tuberculose pulmonar comprovada atraves do encontro do B.A.A.R. em esfregaços de escarro corados pelo Ziehl-Neelsen.. As amostras de sangue foram empregadas, atraves de metodologia adequada, para a determinaçao do perfil hematologico e bioquimico dos tuberculosos em busca de alteraçoes que pudessem ser distribuidas a infeccao. Os resultados observados revelaram uma tendencia a leucocitose (23//dos casos com global acima de 10.000/mm3) e um elevado aumento da velocidade de hemossedimentaçao (86//apresentaram elevaçao com media de 72 a 44 mm para mulheres ehomens, respectivamente). A monocitose, referida por varios autores na tuberculose ativa, nao foi observada. Quanto ao perfil bioquimico, os resultados da determinaçao de fosfatase alcalina e valores obtidos de globulinas se mostraram elevados em 46//dos casos. Esses resultados representaram dados preliminares obtidos atraves das avaliaçoes hematologicas e bioquimicas de pacientes com tuberculose,realizadas antes do emprego da terapeutica recomendada. Estes pacientes representam uma amostragem adequadamente selecionada para a primeira etapa do projeto depesquisa sobre a avaliaçao da conduta farmacoterapeutica no setor publico, com aparticipaçao integrada dos Departamentos de Farmacia Social, Produtos Farmaceuticos e Analises Clinicas e Toxicologicas da Faculdade de Farmacia da UFMG.