阿糖腺苷毫微囊的药代动力学研究

建立了反相HPLC测定血浆中阿糖腺苷的方法。研究和比较了阿糖腺苷溶液型注射剂和毫微囊型注射剂在家兔体内的药代动力学。毫微囊使阿糖腺苷在体液中维持较高的浓度和较长的时间。

Studies on pharmacokinetics of 9-beta-D-arabinofuranosyl adenine nanocapsules]

A method to determine the concentration of Ara-a in plasma by reversed phase high performance liquid chromatography is established. The method offers the advantage of rapid and simple preparation of plasma samples and sampling volumes as small as 0.5 ml. There is no need to extract Ara-A (adenine arabinoside) or to remove or modify sugar moieties to obtain samples of adequate separation. In pharmacokinetic studies, when amounts of clinical material are small and large numbers of assay are required, the present method is very useful. The calibration curve is linear for a wide range of concentration. The recovery is 87.5%. After a single dose of Ara-A-NC adenine arabinoside nanocapsules or Ara-A injection via intravenous administration in rabbits, the Ara-A concentration in plasma was determined by this method. The pharmaceutical parameters of Ara-A-NC and Ara-A injections were obtained by using PKBP-N1 program in NEC computer. The data obtained fitted an open two-compartment model well with two correlation coefficients more than 0.99. In mice given Ara-A injection a shorter elimination half-time (20.32 min), MRT (9.647 min) and a smaller AUC (233.4 micrograms.min.ml-1) were obtained compared with the group given Ara-A-NC injection. For the latter, the figures were 67.82 min, 156.7 min and 309.9 micrograms.min.ml-1, respectively. It can be concluded that NC can alter the pharmacokinetic behavior of Ara-A in mice significantly and keep the drug at a higher level and for a longer time.