2005
DOI: 10.1124/dmd.105.006122
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Role of Mrp2 in the Hepatic Disposition of Mycophenolic Acid and Its Glucuronide Metabolites: Effect of Cyclosporine

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Cited by 99 publications
(79 citation statements)
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References 34 publications
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“…In our rat studies, the acyl glucuronide also represented a minor metabolite, accounting for less then approximately 5% of total glucuronides (data not shown), in agreement with formation rates in perfused rat liver (Westley et al, 2006). Some researchers, however, have proposed that even though the acyl glucuronide is a minor metabolite, it could play a role in MMF GI side effects and therapeutic efficacy (Shipkova et al, 2002).…”
Section: Discussionsupporting
confidence: 59%
See 1 more Smart Citation
“…In our rat studies, the acyl glucuronide also represented a minor metabolite, accounting for less then approximately 5% of total glucuronides (data not shown), in agreement with formation rates in perfused rat liver (Westley et al, 2006). Some researchers, however, have proposed that even though the acyl glucuronide is a minor metabolite, it could play a role in MMF GI side effects and therapeutic efficacy (Shipkova et al, 2002).…”
Section: Discussionsupporting
confidence: 59%
“…6) may result from elevated transport or enhanced generation of MPAG in the male rats. Although evidence that MPAG is excreted into the bile by MRP2 (Kobayashi et al, 2004) was recently confirmed using TRϪ rats (Westley et al, 2006), studies have not observed differences in hepatic MRP2 mRNA levels between male and female rats at 3 months of age and older (Johnson et al, 2002). Thus, it would seem that the increased excretion of MPAG into the bile of male rats is the direct result of increased formation of the metabolite rather than increased transport in the male rats.…”
Section: Discussionmentioning
confidence: 88%
“…Mrp2, a transport protein localized on the hepatic canalicular plasma membrane, is responsible for the biliary excretion of organic anions as well as numerous drugs including pravastatin, vincristine and etoposide Kawabe et al, 1999;Konig et al, 1999;Sasaki et al, 2002). Animals with hereditary conjugated hyperbilirubinemia [Mrp2-deficient rats (TR − ) and Eisai hyperbilirubinemic rats (EHBR)] have been used extensively to examine the substrate specificity and in vivo function of Mrp2 (Westley et al, 2006;ZamekGliszczynski et al, 2006). Patients with Dubin-Johnson syndrome lack MRP2 and hence suffer from hereditary conjugated hyperbilirubinemia (Paulusma et al, 1997).…”
Section: Introductionmentioning
confidence: 99%
“…Using TR Ϫ rats, a strain of mutant Wistar rats lacking the Mrp2 transporter (Soroka et al, 2001) Mrp2 has been shown to be the key transporter involved in MPAGe biliary excretion in rats (Kobayashi et al, 2004;Hesselink et al, 2005;Westley et al, 2006). We have previously reported that in perfused TR Ϫ rat livers, the clearance (CL) and hepatic extraction ratio of MPA were significantly lower compared with control Wistar rats (Westley et al, 2006). One possible mecha-nism for this observation is that there was a difference in the capacity of the TR Ϫ rats to metabolize MPA compared with the control Wistar rats in situ.…”
mentioning
confidence: 99%