Search

Attempts to improve low absorption and rapid metabolic conversion of curcumin were made by developing curcumin-loaded bilayer nanoliposomes coated with chitosan and alginate for intestinal-specifc drug delivery. A curcumin-loaded nanoliposome was prepared with optimized formulations with phosphatidylcholine, curcumin, chitosan, and alginate. The particle size of the optimized formulation was approximately 400 nm, and the encapsulation efciency was more than 99%. In the in vitro release study, curcumin release from the curcumin-loaded nanoliposome with double layers of chitosan/alginate (CNL-CH/AL) was suppressed in the simulated gastric fuid (SGF, pH 1.2) and enhanced in the simulated intestinal fuid (SIF, pH 6.8). In the in vivo pharmacokinetic study in rats, the CNL-CH/AL-treated group showed a prolonged absorption pattern of curcumin and the area under the plasma concentration–time curve from 0 to 24 h (AUC0–24) was improved 109- fold compared to the control group treated with a curcumin solution without a nanocarrier. [ABSTRACT FROM AUTHOR]

• Meloxicam is a substrate for the CYP2C9 and CYP3A4 enzymes. • We have previously reported that the frequency of the CYP2C9*1/*13 genotype in the Korean population is 1.1%. • The CYP2C9*1/*13 genotype is associated with decreased metabolism and increased pharmacodynamic effects of meloxicam. • This is the first report that evaluates the in vivo effects of the CYP2C9*13 allele on the pharmacokinetics and pharmacodynamics of CYP2C9 substrates with a sufficient sample size. To determine the effects of the CYP2C9*1/*13 genotype on the pharmacokinetics and pharmacodynamics of meloxicam in Korean subjects. Meloxicam (15 mg) was orally administered to 21 healthy Korean volunteers with either the CYP2C9*1/*1 or the CYP2C9*1/*13 genotype. Plasma meloxicam concentrations were analysed by HPLC-UV for 72 h after drug administration. The pharmacodynamic effects of meloxicam were determined by measuring TXB generated in blood. The AUC(0,∞) and C of meloxicam were 2.43- and 1.46-fold higher in the CYP2C9*1/*13 group than in the CYP2C9*1/*1 group, respectively. The oral clearance of meloxicam was significantly lower in the CYP2C9*1/*13 group (37.9% of wild type) than in the CYP2C9*1/*1 group. The t of meloxicam was 1.84-fold longer in the CYP2C9*1/*13 group than in the CYP2C9*1/*1 group. The rate of TXB production was significantly lower in the CYP2C9*1/*13 group than in the CYP2C9*1/*1 group. The CYP2C9*1/*13 genotype is associated with decreased metabolism and increased pharmacodynamic effects of meloxicam. [ABSTRACT FROM AUTHOR]

Heme oxygenase-1 (HO-1) catalyses the rate-limiting step of heme degradation to biliverdin, which is in turn reduced to bilirubin, CO and free iron. HO-1 can be induced by several harmful stimuli including oxidative stress, and it has a protective role against the cytotoxicity in different cells. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridinium (MPP+) is a neurotoxic substance that induces the degeneration of dopaminergic neurons. This study examined whether HO-1 can be induced by MPP+ and whether HO-1 has a protective role against the MPP+-induced cytotoxicity in PC-12 cells. MPP+ triggered a relatively rapid induction of HO-1. The MPP+-induced cytotoxicity and reactive oxygen species (ROS) production markedly increased by HO-1 inhibitor, zinc protoporphyrin-IX (ZnPP-IX). The increase of ROS production by ZnPP-IX was completely abrogated by either two products of HO (biliverdin or bilirubin) while the increase of cytotoxicity by ZnPP-IX was attenuated partially. These suggest that HO-1 expression might have some cytoprotective effect against MPP+-induced cytotoxicity. [ABSTRACT FROM AUTHOR]

Aims To determine the frequencies of the variant alleles and the genotypes of CYP2C9 in a Korean population. Methods Three hundred and fifty-eight healthy Korean subjects were studied. CYP2C9 alleles were detected by polymerase chain reaction-restriction fragment length polymorphism assays and direct sequencing assays. Results The allele frequencies were 0.934 for CYP2C9* 1, 0.060 for CYP2C9* 3 and 0.006 for CYP2C9* 13. The CYP2C9*2,* 4,* 5 and * 11 alleles were not detected. The frequencies of the CYP2C9* 1/* 1, * 1/* 3 and * 1/* 13 genotypes were 0.869, 0.120 and 0.011, respectively. Conclusion The frequency of the CYP2C9* 3 allele in the Korean population studied was significantly higher than reported elsewhere, and a novel allele, CYP2C9* 13, was found at a frequency of 0.006 (95% confidence interval 0, 0.012). Only three genotypes of CYP2C9, CYP2C9* 1/* 1,* 1/* 3 and * 1/* 13 were observed in this Korean population. [ABSTRACT FROM AUTHOR]