Previous PhD Janne Backman, currently Professor of Clinical BAY 73-4506 Regorafenib Pharmacology, and Mikko Niemi, a professor of pharmacogenetics at both the University of t of Helsinki, were the most important people and Aufsichtsbeh Earths in some of these studies. In recent years special attention to OATP1B1, in breast cancer resistance protein and Pglycoprotein in pharmacokinetics and drug interactions of statins and oral medication has been placed.Polymorphisms of the gene, the hepatic uptake transporter OATP1B1 affect the SLCO1B1 essential transport function. Human Tr hunter SLCO1B1 variant c.521TC have increased AUC of pravastatin Ht compatible with a reduced hepatic uptake. In a panel study of the homozygous variant genotype had lower mean AUC of SLCO1B1 c.521TC simvastatin Acid 3.2 times, 2.
4 times as atorvastatin, pravastatin and rosuvastatin 1, 9 times 1.7 times h Ago than the Non-Tr hunter, but had no significant effect on the AUC of fluvastatin, or simvastatin parent. Erh Hte risk of myopathy induced by statins k nnte At Tr Be predicted like c.521TC exposed to high doses of simvastatin. The validity of this prediction was best in subsequent clinical trials CONFIRMS. The genotyping of SLCO1B1 variant c.521TC helps to identify those patients with high doses of simvastatin are one obtains Muscular Hten risk Rer toxicity Th Depends on the concentration. C.521CC SLCO1B1 genotype was associated with a significant increase in the AUC of repaglinide, but not nateglinide, rosiglitazone or pioglitazone.
Gene polymorphism was associated with SLCO1B1 as a base rate of synthesis increased Hte cholesterol, fasting was tocholesterol desmosterol ratio Ratio 40% h Ago in healthy individuals with the SLCO1B1 variant genotype c.521CC than in patients with genotype c. 521TT. In addition, many interactions of cyclosporine than with pravastatin and repaglinide may primarily be mediated by inhibition of hepatic uptake transporter OATP1B1. SLCO1B1 variants show marked geographic differences in their frequencies. For example, the low activity of t haplotypes 5 and 15 have a combined frequency south of about 15 to 20% of the Europ He, 10 Asians, 15% and 2% in sub-Saharan Africa. These differences typed k Dinner may have mediated differences in the risk of side effects and interactions by OATP1B1 among various populations.
Polymorphism of the ABCB1 gene, which acts for the glycoprotein efflux pump, P, on the pharmacokinetics of drugs, their substrates. Finland was in man, the frequency of haplotypes c.3435T c.1236T c.2677T and c.1236C c.2677Gc 43%. 3435C was 34%. In subjects with ABCB1 TTT / TTT genotype, exposure to simvastatin Acid 60% was green He atorvastatin and 55% green It than in patients with the genotype of the CGC / CGC, but no differences were found between these genotypes in the pharmacokinetics of its lactone. Furthermore, no significant differences between these two groups of haplotypes in the AUC of fluvastatin, pravastatin, lovastatin, lovastatin S Acid or rosuvastatin given. The gene for BCRP, ABCG2 efflux pump. Finnish in humans, was the frequency of allele c.421A variant about 10%. Patients with genotype c.421AA had a 150% h Here AUC of rosuvastatin and 70% green It as the AUC of atorvastatin