Godawska-Matysik Anna, Kieć-Kononowicz Katarzyna
Jagiellonian University, Medical College, Department of Chemical Technology and Biotechnology of Drugs, Medyczna 9, PL 30-688 Kraków, Poland.
Acta Pol Pharm. 2006 Sep-Oct;63(5):381-5.
Praziquantel (PZQ) is the drug of choice for the treatment of human schistosomiasis. It is estimated that about 200 million people in the world are currently affected by this tropical disease. Now PZQ is also used in malaria treatment. The usefulness of PZQ as antimalarial drug is important because of rapid development of resistance to usually applied drugs. PZQ undergoes extensive metabolism in human body, mainly in liver by two cytochrome P-450 isoenzymes 2B1 and 3A. As the result of these biotransformations numerous mono- and dihydroxylated derivatives in B, C and D ring are formed. Two metabolites have been fully identified and described, as cis- and trans-4-hydroxypraziquantel. Up to now there were created many different in vitro and in vivo models of PZQ biotransformations. In vitro model of PZQ biotransformation was created by using human cytochrome P-450 3A4 expressed in Eschelichia coli and Saccharomyces cerevisiae. In the first experiment we have used human cytochrome P-450 3A4 from Escherichia coli (isolated on NTA-column). In the second experiment microsomes isolated from Saccharomyces cerevisiae containing coexpressed human CYP 3A4, human CYP-reductase and human cytochrome b5 were used. The reactions were monitored by HPLC and MS.
吡喹酮（PZQ）是治疗人类血吸虫病的首选药物。据估计，目前全球约有2亿人受这种热带疾病影响。现在吡喹酮也用于疟疾治疗。由于常用药物耐药性的迅速发展，吡喹酮作为抗疟药物的有效性很重要。吡喹酮在人体中经历广泛的代谢，主要在肝脏中通过两种细胞色素P - 450同工酶2B1和3A进行代谢。这些生物转化的结果是在B、C和D环中形成了许多单羟基和二羟基化衍生物。已完全鉴定和描述了两种代谢物，即顺式和反式4 - 羟基吡喹酮。到目前为止，已经建立了许多不同的吡喹酮生物转化体外和体内模型。通过使用在大肠杆菌和酿酒酵母中表达的人细胞色素P - 450 3A4建立了吡喹酮生物转化的体外模型。在第一个实验中，我们使用了来自大肠杆菌（在NTA柱上分离）的人细胞色素P - 450 3A4。在第二个实验中，使用了从含有共表达的人CYP 3A4、人CYP还原酶和人细胞色素b5的酿酒酵母中分离的微粒体。通过高效液相色谱法（HPLC）和质谱法（MS）监测反应。
