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

ABSTRACT

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