Toxicokinetics versus pi-tarmacokinetics of oral anabolic steroids abused in doping practice

Despite the high prevalence of toxicological profile of oral anabolic steroids, laboratory investigations on toxicokinetic profile of anabolic steroids overdoses have been largely unknown and underestimated. In the present study toxicokinetics of methyltestosterone and testosterone undecanoate were studied in male adult rats after oral administration of single toxic dose to explore possible alteratiolls in their pharmacokinetic behavior in comparison to their corresponding parameters at therapeutic doses. The extraction methods adapted for plasma samples showed mean recoveries of 87.4+0.19% and 103.5 +/- 0.1% for methyltestosterone and testosterone undecanoate respectively. Inter- and intra-day precision were 2.4 -8.7% coefficient of variance [CV.], and 4.3 -2.8% [CV.] for methyltestosterone and testosterone undecanoate respectively. Plasma concentrations measured by high performance liquid chromatography method was applied for the analysis of both methyltestosterone and testosterone undecanoate with high sensitivity and low detection limit of 1ng/ml. The pharmacokinetic parameters were estimated using non-compartmental method. Both drugs showed non-linear pharmacokinetic behavior represented in disproportional increase in C[max], AUC[0-infinity] and increase in V, CI, t1/2 and lambda. The present data indicate accumulation of steroids in tissues leading to severe toxicological consequences

Comparative in vivo and in vitro hepato-toxicity studies for oral anabolic steroids abused in sports

Studies on hepatotoxicity of anabolic- androgenic steroids in experimental animals and in controlled clinical studies were based on the use of doses at substantially lower level than those practiced by the abusers. the aim of this study was to investigate acute hepatotoxic effects after administration of suprapharmacological doses to experimental animals as well as to isolated hepatocytes suspension to reflect any hepatic dysfunction caused by anabolic steroid abuse. Male adult albino rats were administered daily oral doses of methyltestosterone [175mg/Kg], testosterone-undecanoate [420 mg/Kg], and their combination for 7 days. In vivo results showed significant increase in serum aspartate aminotransferase [AST] and lactate dehydrognease [LDU]. While both steroids did not affect serum levels of alanine aminotransferase [ALT], thiobarbituric acid reactive substances [TBARS], reduced glutathione levels and total protein, when administered either individually or in combination. Leakage of ALT, AST and LDH was observed in any vitro studies in addition to increase in TBARS content. All treatments did not result in any significant difference in reduced glutathione content compared to the respective control. Histopathological examination of the liver revealed inflammatory and degenerative lesions in addition to focal necrosis. The histopathological findings confirm the biochemical studies [both in vivo and in vitro] and show clear toxic manifestations of suprapharmacological doses of theses anabolies on the liver