title: Biotransformation of praziquantel by human cytochrome p450 3A4 (CYP 3A4).
abstract: 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.
authors.affiliation: Jagiellonian University, Medical College, Department of Chemical Technology and Biotechnology of Drugs, Medyczna 9, PL 30-688 Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Godawska-Matysik
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kieć-Kononowicz
mesh_terms: D000871:Anthelmintics; D000962:Antimalarials; D001711:Biotransformation; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D015786:Cytochromes b5; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D008861:Microsomes / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase; D011223:Praziquantel / Q000493:pharmacokinetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: D000871:Anthelmintics; D000962:Antimalarials; D011223:Praziquantel; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D009251:NADPH-Ferrihemoprotein Reductase