OBJECTIVETo report the pharmacokinetic parameters of helicid HD in rats after intravenous administration at different doses.

METHODFifteen Wistar rats were randomly assigned as three groups (n=5, male) to be given helicid solution via tail vein injection at a single dose of 2.23, 4.46, 6.70 mg x kg(-1), respectively. Blood samples were collected via tail vein at time intervals after HD injection. 6% perchloric acid was to precipitate plasma protein. Separation was achieved on a reversed-phase C18 column with UV detection at 270 nm.

RESULTThe calibration curves were linear ranging from 43.8 to 43,800 microg x L(-1). The intra-and inter-day precisions were no more than 6%. The average recovery of helicid was more than 87% from plasma. With minimum akaike information criterion (AIC) values, a two-compartment open pharmacokinetic model was proposed and validated through the DAS 2.0 to explain the apparent diphasic phenomenon of (HD) in rat blood after intravenous administration. Helicid appeared to be distributed rapidly into a highly perfused central compartment (first compartment), with a less rapidly elimination. The diphasic phenomenon could be observed from the compartment model parameters t(1/2alpha) and t(1/2beta). The least squares regression analysis indicated that the plasma concentrations and AUC of helicid in rat plasma were proportional to the administrated doses. At the administrated doses of 2.23, 4.46, 6.70 mg x kg(-1), the values of distribution half-life (t(1/2alpha)) were 4.582, 5.097, 4.727 min, respectively. And the values of elimination half-life (t(1/2beta)) were 23.945, 26.508 and 25.396 min, respectively. The volume of distribution from these three different doses were 0.036, 0.035, 0.035 L, respectively. The AUCo(0-->t) (area under the concentration-time curve) increase was proportional to the administrated dose.

CONCLUSIONIn the range of the doses examined, the pharmacokinetics of helicid in rats is based on linear dynamics.