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Effects of UGT1A1*28 polymorphism on raloxifene pharmacokinetics and pharmacodynamicsTrontelj, Jurij ...ABSTRACT Aims Raloxifene concentrations were reported to approximately correlate with serum bilirubin levels. Bilirubin is a typical UGT1A1 substrate. Based on these facts, we postulated a hypothesis ... that UGT1A1 is the key enzyme for metabolic clearance of raloxifene and that the common UGT1A1*28 polymorphism significantly contributes to the large pharmacokinetic variability of raloxifene. Methods Serum samples from postmenopausal osteoporotic patients treated with raloxifene were assayed for the concentrations of raloxifene and its glucuronides by LC-MS-MS. The same samples were also genotyped for the presence of UGT1A1*28 polymorphism by the SSCP method. The pharmacodynamic effect was evaluated by measuring the change in bone mineral density (BMD) in femoral neck, hip and lumbar spine after 12 months of raloxifene therapy Results Patients homozygous for the *28 allele showed a significantly, two-fold higher raloxifene glucuronide concentrations compared to the hetero- and homozygotes for the wild-type allele: (558 115) nmol/L compared to (295 43) nmol/L, respectively, p=0.012. This indicates a higher raloxifene exposure in the *28/*28 group. Consequently, a significantly greater increase in hip BMD was observed in subjects homozygous for the *28 allele compared to the group carrying at leastone copy of the wild-type allele: (4.4 2.4) % compared to (0.3 1.4) %, p=0.035. Conclusions In this study it was shown that a relatively commonUGT1A1*28 polymorphism may considerably influence raloxifene pharmacokinetics and pharmacodynamics. Underlying mechanisms and clinical implications of our findings are also discussed.Vir: British journal of clinical pharmacology. - ISSN 0306-5251 (Vol. 67, no. 4, 2009, str. 437-444)Vrsta gradiva - članek, sestavni delLeto - 2009Jezik - angleškiCOBISS.SI-ID - 2510705
Avtor
Trontelj, Jurij |
Marc, Janja |
Zavratnik, Andrej |
Bogataj, Marija, 1963- |
Mrhar, Aleš
Teme
UGT1A1*28 |
raloksifen |
osteoporoza |
polimorfizem
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vir: British journal of clinical pharmacology. - ISSN 0306-5251 (Vol. 67, no. 4, 2009, str. 437-444)
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Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Trontelj, Jurij | 23420 |
Marc, Janja | 12189 |
Zavratnik, Andrej | 23785 |
Bogataj, Marija, 1963- | 11124 |
Mrhar, Aleš | 06086 |
Vir: Osebne bibliografije
in: SICRIS
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