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Intestinal cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) both play a vital role in the metabolism of oral cyclosporine (CsA). We investigated the genetic polymorphisms in CYP3A4(promoter region and exons 5, 7 and 9) and MDR1 (exons 12, 21 and 26) genes and the impact of these polymorphisms on the pharmacokinetics of oral CsA in stable heart(More)
The MDR1 multidrug transporter plays a key role in determining drug bioavailability, and differences in drug response exist amongst different ethnic groups. Numerous studies have identified an association between the MDR1 single nucleotide polymorphism (SNP) exon 26 3435C>T and differences in MDR1 function. We performed a haplotype analysis of the MDR1 gene(More)
BACKGROUND Systemic exposure to rosuvastatin had been observed to be approximately 2-fold higher in Japanese subjects living in Japan compared with white subjects in Western Europe or the United States. The organic anion transporting polypeptide 1B1 contributes to the hepatic uptake of rosuvastatin. Polymorphisms in the SLCO1B1 gene can lead to reduced(More)
There is a worldwide increasing use of herbs which are often administered in combination with therapeutic drugs, raising the potential for herb-drug interactions. St John's wort (Hypericum perforatum) is one of the most commonly used herbal antidepressants. A literature search was performed using Medline (via Pubmed), Biological Abstracts, Cochrane Library,(More)
The Singapore Genome Variation Project (SGVP) provides a publicly available resource of 1.6 million single nucleotide polymorphisms (SNPs) genotyped in 268 individuals from the Chinese, Malay, and Indian population groups in Southeast Asia. This online database catalogs information and summaries on genotype and phased haplotype data, including allele(More)
The MDR1 multidrug transporter regulates the traffic of drugs, peptides and xenobiotics into the body as well as sensitive tissues like the brain, germ cells and the developing fetus. Hence, it may influence an individual's response to drugs as well as his/her susceptibility to complex diseases in which environmental factors, especially xenobiotics, play a(More)
PURPOSE To characterize pregnane X receptor (PXR) polymorphic variants in healthy Asian populations [Chinese, Malay and Indian (n=100 each)], and to investigate the association between PXR haplotypes and hepatic mRNA expression of PXR and its downstream target genes, CYP3A4 and ABCB1, as well as their influence on the clearance of doxorubicin in Asian(More)
The influence of three high frequency ABCB1 polymorphisms (c.1236C>T, c.2677G>A/T, and c.3435C>T) and the ABCG2 c.421C>A polymorphism on the disposition of doxorubicin in Asian breast cancer patients receiving adjuvant chemotherapy was investigated in the present study. The allelic frequency of the ABCB1 c.1236T, c.2677T, c.2677A, and c.3435T variants were(More)
AIMS To investigate the frequency of the single nucleotide polymorphism C3435T in exon 26 of the MDR1 gene in Asians and to determine the functional significance of this SNP with the clinical pharmacokinetics of oral cyclosporin (Neoral) in 10 stable heart transplant patients. METHODS The MDR1 C3435T polymorphism was investigated in 290 healthy Asian(More)
The present study aimed to identify polymorphic genes encoding carbonyl reductases (CBR1, CBR3) and investigate their influence on doxorubicin disposition in Asian breast cancer patients (n = 62). Doxorubicin (60 mg/m(2)) was administered every 3 weeks for four to six cycles and the pharmacokinetic parameters were estimated using non-compartmental analysis(More)