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 it 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 [1]. As the result of these biotransformations numerous mono- and dihydroxylated derivatives in B, C and D ring are formed. One metabolite has been fully identified and described, it is cis- and trans- 4-hydroxypraziquantel [2,3]. Up to now there were created many different in vitro and in vivo models of PZQ biotransformations[4]. In our research we have created in vitro model of PZQ biotransformation by using of human cytochrome P-450 3A4 expressed in Escherichia coli[5] and Saccharomyces cerevisiae[6].

In the first experiment was used human cytochrome P-450 3A4 from Escherichia coli (isolated on Ni-NTA-column). In the second experiment we used microsomes isolated from Saccharomyces cerevisiae containing coexpressed human CYP 3A4, human CYP-reductase and human cytochrome b5. The reactions were monitored by HPLC and MS.

The research suppotred by Polish State Committee for Scientific Research, grant no. 2 P05F 005 28

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[1]. Ridtitid W., Wongnawa M., Mahatthanatrakul W., Panyo J., Sunbhainch M., Clin. Pharm. Therap., 2002, 72(5),505-513

[2] K. Kieć-Kononowicz, Z.S. Farghaly, G. Blaschke, Arch. Pharm (Weinheim), 1991, 324, 235-237

[4]. Azerad R., Adv. Biochem. Engin. Biotechnol., 1999, 63, 169-218

[5]. Gillam E.M.J., Baba T., Kim B.R., Ohmori S., Guengerich F.P., Arch. Biochem. Biophys, 1993, 305, 123-131

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