Age effects on the pharmacokinetics of tityustoxin from Tityus serrulatus scorpion venom in rats. 2004

E A Nunan, and V Arya, and G Hochhaus, and V N Cardoso, and T Moraes-Santos
Laboratório de Controle de Qualidade, Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.

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 microg) 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.

UI MeSH Term Description Entries
D007279 Injections, Subcutaneous Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin. Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D008297 Male Males
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D000367 Age Factors Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time. Age Reporting,Age Factor,Factor, Age,Factors, Age
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012604 Scorpion Venoms Venoms from animals of the order Scorpionida of the class Arachnida. They contain neuro- and hemotoxins, enzymes, and various other factors that may release acetylcholine and catecholamines from nerve endings. Of the several protein toxins that have been characterized, most are immunogenic. Scorpion Toxin,Scorpion Toxins,Scorpion Venom Peptide,Tityus serrulatus Venom,Scorpion Venom,alpha-Scorpion Toxin,beta-Scorpion Toxin,gamma-Scorpion Toxin,Peptide, Scorpion Venom,Toxin, Scorpion,Toxin, alpha-Scorpion,Toxin, beta-Scorpion,Venom Peptide, Scorpion,Venom, Scorpion,Venom, Tityus serrulatus,alpha Scorpion Toxin,beta Scorpion Toxin,gamma Scorpion Toxin
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D019540 Area Under Curve A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992) AUC,Area Under Curves,Curve, Area Under,Curves, Area Under,Under Curve, Area,Under Curves, Area

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