Raloxifene glucuronide standards were synthesized by human recombinant enzymes and isolated, purified and charcterized by LC-MS/MS. The developed method was validated for an accurate and precise quantification of raloxifene and its two glucuronides in only 500 microliters of human plasma or serum with a limit of quantification for raloxifene of just 88 pg/mL.
COBISS.SI-ID: 2107505
Until now, raloxifene transport and metabolism have not been studied adequately, even though they strongly affect raloxifene pharmacokinetics. Therefore, human and porcine liver and intestinal microsomes and diffusion chambers were used to adress this issue. The results showed a pronounced similarity between human and porcine raloxifene conjugation kinetics in intestinal microsomes and a very high metabolic clearance both in liver and intestinal microsomes. Our results explain the extremely low bioavailability of raloxifene (<2%) and its slow intestinal absorption.
COBISS.SI-ID: 2382705
In order to study raloxifene pharmacokinetics in vivo, a new assay was developed and validated for determination of raloxifene and its two metabolites M1 and M2 in human plasma and serum. The method is based on solid phase extraction (SPE) and liquid chromatography with tandem mass spectrometry (LC-MS-MS).
COBISS.SI-ID: 2415729
Subjects with UGT1A1*28 genotype exhibited a twofold higher raloxifene exposure compared to hetero- and homozygotes for the wild-type allele. This indicates that raloxifene pharmacokinetics is very likely affected by the UGT1A1*28 polymorphism. It was also demonstrated that *28 homozygotes gained a significantly greater increase in hip bone mineral density after 12 months of raloxifene treatment.
COBISS.SI-ID: 2510705
In the article a double Weibull model was developed to describe different patterns of gastric emptying of pellets. This model connects process of gastric emptying of multiunit drug delivery systems with processes of drug release, absorption and presystemic metabolism. Moreover, this concept can be successfully applied also to singleunit drug delivery systems, such as film-coated tablet in which raloxifene is administered. By the aid of the developed approach, biorelevant in vitro drug release test will be developed to improve prediction of drug delivery systems behaviour in in vivo situations.
COBISS.SI-ID: 2517361