Effects of ursodeoxycholic acid on P-glycoprotein and cytochrome P450 3A4–dependent pharmacokinetics in humans

Abstract

Under the conditions in our study, UDCA only modestly decreased digoxin disposition without detectable changes in midazolam pharmacokinetics. The clinical relevance of these findings remains to be determined.

Effect of ursodeoxycholic acid on bile acid profiles and intestinal detoxification machinery in primary biliary cirrhosis and health

“…Here, we observed duodenal induction of P-glycoprotein by UDCA in patients with PBC as well as in healthy subjects. The effect of UDCA on P-glycoprotein-dependent clinical pharmacokinetics has been previously investigated using an established probe drug, digoxin [33]. In eight healthy volunteers, UDCA at a daily dose of 13 mg/kg decreased absolute bioavailability of oral digoxin from 77% to 70% (mainly based on abridged AUC 0-4 h ) but UDCA had no significant effect on other pharmacokinetic parameters of digoxin including AUCs calculated over periods longer than 4 h. Our results suggest that the effects of therapeutic doses of UDCA on P-glycoprotein strengthen tissue defense and the absorption barrier against xenobiotics.…”

Effect of ursodeoxycholic acid treatment on the expression and function of multidrug resistance-associated protein 2 in rat intestine

“…As described above, UDCA would affect the expression of efflux transporters in the intestine, but the information concerning the effect of UDCA treatment on the function of efflux transporters in the intestine is quite lacking. In addition, there are some human studies indicating that UDCA would affect the intestinal absorption of drugs such as cyclosporine A and digoxin, but the precise mechanisms are still unknown 17, 25. In the present study, we examined the effect of UDCA on in vitro and in vivo functions of the intestinal Mrp2 in rats, in relation to its effect on the expression of the transporter.…”

“…UDCA is a hydrophilic bile acid currently used for the treatment of cholestatic liver disease such as primary biliary cirrhosis 12, 14. Like other bile acids, UDCA is known to affect the expression of various hepatobiliary transporters and enzymes involved in bile acid synthesis and detoxification 15–17. In mice, UDCA is reported to stimulate the expression of efflux transporters such as Mrps not only in the liver, but also in the intestine and the kidney 15.…”

“…On the other hand, Fickert et al16 reported that UDCA feeding (1% wt/wt, 7 days) on mice induced the expression of canalicular Bsep, in addition to Mrp2. They also showed that UDCA feeding induced canalicular mdr1a/b, while Becquemont et al17 reported that UDCA had no effect on MDR1 expression in LS174T cells. Thus, though there are some studies on the effect of UDCA on the expression of efflux transporters, the results are still controversial.…”

Statins and Ursodeoxycholic Acid: Cooperation or Neutrality?

“…Потенциальные индукторы CYP3А4 могут значительно снижать концентрацию симвастатина Статины и урсодезоксихолевая кислота Литература и ловастатина [32]. УДХК не оказывает заметного влияния на экспрессию Р-гликопротеина и CYP3A4 [33]. УДХК улучшает кинетику розувастатина, значительно снижая его клиренс посредством ингибирования ак-тивности OATP1B1 путем ингибирования транскрип-ционного ядерного фактора гепатоцитов HNF alpha [34].…”