Minipig as a model for drug metabolism in man: comparison of in vitro and in vivo metabolism of propafenone.
To prove the suitability of minipigs as experimental animal in modeling of the drug metabolism and pharmacokine-tics in man, propafenone metabolism in vitro at the microsomal level as well as propafenone pharmacokinetics in the minipig was studied. The results were compared with those obtained for humans. It can be concluded that whereas the microsomal in vitro system of minipig may be a good model for drug metabolism in the man, the pharmacokinetics in the whole organism is more complex reflecting differences in substrate specificities of many enzymatic and transport systems. In this particular case, it has been documented that the glucuronidation of propafenone principal metabolite (5-hydroxypropafenone) is more efficient in the minipig.
Anzenbacherová
Eva
E
Institute of Medical Chemistry and Biochemistry, Faculty of Medicine, Palacky University, Olomouc, Czech Republic.
Anzenbacher
Pavel
P
Svoboda
Zbynek
Z
Ulrichová
Jitka
J
Kvetina
Jaroslav
J
Zoulová
Jana
J
Perlík
Frantisek
F
Martínková
Jirina
J
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism; D023421:Models, Animal; D011405:Propafenone / Q000493:pharmacokinetics*; D013552:Swine; D013556:Swine, Miniature
D000889:Anti-Arrhythmia Agents; D011405:Propafenone