Park Sang Hyun, Pradeep Kannampalli
Radiation Research Division for Biotechnology, Korea Atomic Energy Research Institute, 1266 Shinjeong-dong, Jeongeup, Jeonbuk 580-185, South Korea.
J Biomed Biotechnol. 2010;2010:590707. doi: 10.1155/2010/590707. Epub 2010 Mar 31.
The main objective of this investigation was to determine the absorption, distribution, excretion, and pharmacokinetics of the antimalarial drug pyronaridine tetraphosphate (PNDP) in Sprague-Dawley rats. Following oral administration of a single dose (10 mg/Kg) of 14C-PNDP, it was observed that the drug was readily absorbed from the small intestine within 1 hour following oral administration and was widely distributed in most of the tissues investigated as determined from the observed radioactivity in the tissues. The peak value of the drug in the blood was reached at around 8 hours postadministration, and radioactivity was detected in most of the tissues from 4 hours onwards. 14C-PNDP showed a poor permeability across the blood-brain barrier, and the absorption, distribution, and excretion of 14C-PNDP were found to be gender-independent as both male and female rats showed a similar pattern of radioactivity. Excretion of the drug was predominantly through the urine with a peak excretion post 24 hours of administration. A small amount of the drug was also excreted in the feces and also in the breath. It was found that the C(max), AUC (0-inf), and T(max) values were similar to those observed in the Phase II clinical trials of pyronaridine/artesunate (Pyramax) conducted in Uganda.
本研究的主要目的是测定抗疟药物磷酸咯萘啶（PNDP）在斯普拉格-道利大鼠体内的吸收、分布、排泄及药代动力学。口服单剂量（10 mg/Kg）的14C-PNDP后，观察到药物在口服给药后1小时内即从小肠迅速吸收，并根据组织中观察到的放射性确定其广泛分布于大多数研究的组织中。给药后约8小时达到血药峰值，4小时后在大多数组织中检测到放射性。14C-PNDP在血脑屏障中的通透性较差，且发现14C-PNDP的吸收、分布和排泄与性别无关，因为雄性和雌性大鼠的放射性模式相似。药物排泄主要通过尿液，给药24小时后排泄达到峰值。少量药物也通过粪便和呼出气体排泄。发现C(max)、AUC(0-inf)和T(max)值与在乌干达进行的磷酸咯萘啶/青蒿琥酯（Pyramax）II期临床试验中观察到的值相似。
