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To evaluate whether alterations in the multidrug-resistance (MDR)-1 gene correlate with intestinal MDR-1 expression and uptake of orally administered P-glycoprotein (PGP) substrates, we analyzed the MDR-1 sequence in 21 volunteers whose PGP expression and function in the duodenum had been determined by Western blots and quantitative immunohistology (n = 21)(More)
BACKGROUND P-glycoprotein, the gene product of MDR1, confers multidrug resistance against antineoplastic agents but also plays an important role in the bioavailability of common drugs in medical treatment. Various polymorphisms in the MDR1 gene were recently identified. A silent mutation in exon 26 (C3435T) was correlated with intestinal P-glycoprotein(More)
Cytochrome P450 2D6 (CYP2D6) metabolizes many important drugs. CYP2D6 activity ranges from complete deficiency to ultrafast metabolism, depending on at least 16 different known alleles. Their frequencies were determined in 589 unrelated German volunteers and correlated with enzyme activity measured by phenotyping with dextromethorphan or debrisoquine. For(More)
AIMS The cytochrome P450 enzyme CYP1A2 metabolises several drugs and carcinogens. We wanted to determine how much of the variability of CYP1A2 activity is explained by a newly discovered gene polymorphism in intron 1. METHODS A single nucleotide polymorphism in intron 1 of the CYP1A2 gene at position 734 downstream of the first transcribed nucleotide was(More)
The polymorphic arylamine N-acetyltransferase (NAT2; EC is supposed to be a susceptibility factor for several drug side effects and certain malignancies. A group of 844 unrelated German subjects was genotyped for their acetylation type, and 563 of them were also phenotyped. Seven mutations of the NAT2 gene were evaluated by allele-specific PCR(More)
The frequency of functionally important mutations and alleles of genes coding for xenobiotic metabolizing enzymes shows a wide ethnic variation. However, little is known of the frequency distribution of the major allelic variants in the Russian population. Using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) genotyping assays(More)
OBJECTIVE Extracts of St John's wort (Hypericum perforatum) are widely used in the treatment of depression, often as an over-the-counter drug. In contrast to its frequent use, knowledge about the pharmacokinetics of ingredients and drug interactions of St John's wort is poor. We studied the interaction between hypericum extract LI160 and digoxin. METHODS(More)
OBJECTIVE We compared the pharmacogenetic effects of OATP-C (organic anion transporting polypeptide C) *1a, *1b (A388G), and *5 (T521C) haplotypes on single-dose pharmacokinetics of pravastatin in white subjects. METHODS Thirty healthy white male subjects were grouped according to their OATP-C haplotype. Each group contained 10 individuals who were either(More)
This study reports a C-->A transversion at position 4887 in exon 7 of cytochrome P4501A1 (CYP1A1), resulting in a threonine-asparagine exchange in codon 461. The polymorphism is located directly beside the known codon 462-Ile/Val mutation (m2) near the heme binding region. The C4887A mutation leads to the loss of a BsaI cleavage site, which allows analysis.(More)
AIMS The genetically polymorphic cytochrome P450 enzyme CYP2C9 metabolizes many important drugs. We studied the frequency of the amino acid variants cysteine144 (CYP2C9*2 ) and leucine359 (CYP2C9*3 ) in a Turkish population and the correlation between genotype and phenotype using phenytoin as probe drug. METHODS CYP2C9 alleles *2 and *3 were measured in(More)