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The hepatic uptake of pitavastatin is mediated by carriers, especially OATP1B1, which is encoded by the SLCO1B1 gene. Because the liver is a target organ of pitavastatin, OATP1B1 is responsible for both the pharmacological effects and clearance of pitavastatin. The effects of the SLCO1B1*15 allele on the pharmacokinetics (PK) of pitavastatin were studied. Pitavastatin 2 mg was orally administered to 38 subjects with SLCO1B1*1a/*1b (n = 20), *1b/*15 (n = 13), or *15/*15 (n = 5). After pitavastatin administration, the plasma concentrations of pitavastatin and pitavastatin lactone were assayed for up to 48 h using liquid chromatography-tandem mass spectrometry. In comparison to the SLCO1B1*1a/*1b subjects, only a Cmax was slightly higher in the SLCO1B1*1b/*15 subjects. However, the SLCO1B1*15/*15 subjects had a 1.74-fold higher AUCinf (285.5 ± 14.5 vs. 164.6 ± 41.3 ng·h/mL; p < 0.001), a 2.21-fold higher Cmax (106.7 ± 15.1 vs. 48.3 ± 13.4 ng/mL; p < 0.001), and a 47.3% lower apparent oral clearance (13.1 ± 3.9 vs. 6.9 ± 0.4 L/h; p < 0.001) of pitavastatin. For pitavastatin lactone, there were no significant differences in AUCinf, Cmax, t1/2, and tmax among the three genotypes. Unlike previous studies, the disposition of pitavastatin exposure was not altered in subjects with the SLCO1B1*1b/*15 genotype, except Cmax. However, pitavastatin exposure was significantly increased in subjects with the SLCO1B1*15/*15 genotype due to reduced hepatic absorption. [ABSTRACT FROM AUTHOR]

Lornoxicam is extensively metabolized by CYP2C9, and a CYP2C9*13 is one of the principal variant alleles in East Asian populations. The aim of this study was to evaluate the effects of CYP2C9*1/*13 on the pharmacokinetic parameters of lornoxicam in healthy individuals. A single oral dose of 8 mg lornoxicam was given to 22 Korean volunteers with different CYP2C9 genotypes (8, 8 and 6 carriers of CYP2C9*1/*1, *1/*3 and *1/*13 genotypes, respectively). Lornoxicam and 5′-hydroxylornoxicam levels were analysed using HPLC-UV in plasma samples collected up to 24 hr after taking the drug. In individuals with CYP2C9*1/*13, lornoxicam had a higher Cmax ( p < 0.001), a longer half-life ( p < 0.001), a lower oral clearance ( p < 0.001) and a higher area under the plasma concentration-time curve from zero to infinity (AUCinf) than in CYP2C9*1/*1 individuals ( p < 0.001). The Cmax and AUCinf of 5′-hydroxylornoxicam were lower in CYP2C9*1/*13 individuals than in CYP2C9*1/*1 individuals, but the half-life of 5′-hydroxylornoxicam did not differ between the two groups. The half-life, oral clearance and AUCinf of lornoxicam were similar in individuals with CYP2C9*1/*13 and those with CYP2C9*1/*3. The Cmax, half-life and AUCinf of 5′-hydroxylornoxicam were also similar in both groups, although Cmax was higher in CYP2C9*1/*13 individuals ( p < 0.01). A CYP2C9*1/*13 genotype markedly reduced the conversion of lornoxicam to 5′-hydroxylornoxicam, to a similar extent as that observed with the CYP2C9*1/*3 genotype. [ABSTRACT FROM AUTHOR]

Aim:CYP2C9 enzyme metabolizes numerous clinically important drugs. The aim of this study is to investigate the frequencies of CYP2C9 genotypes and the effects of selected alleles on losartan pharmacokinetics in a large sample of the Korean population.Methods:The CYP2C9 gene was genotyped in 1796 healthy Korean subjects. CYP2C9 alleles (CYP2C9*1, *2, *3 and *13 alleles) were measured using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and direct sequencing assay. The enzymatic activity of each CYP2C9 genotype was evaluated using losartan as the substrate.Results:The frequencies of CYP2C9*1, *3 and *13 allele were 0.952 (95% confidence interval 0.945-0.959), 0.044 (95% CI 0.037-0.051) and 0.005 (95% CI 0.003-0.007), respectively. The frequencies of the CYP2C9*1/*1, *1/*3, *1/*13 and *3/*3 genotypes were 0.904 (95% CI 0.890-0.918), 0.085 (95% CI 0.072-0.098), 0.009 (95% CI 0.005-0.013) and 0.001 (95% CI 0.000-0.002), respectively. In the pharmacokinetics studies, the AUC0-∞ of losartan in CYP2C9*3/*3 subjects was 1.42-fold larger than that in CYP2C9*1/*1 subjects, and the AUC0-∞ of E-3174, a more active metabolite of losartan, in CYP2C9*3/*3 subjects was only 12% of that in CYP2C9*1/*1 subjects.Conclusion:The results confirmed the frequencies of CYP2C9 genotypes in a large cohort of Koreans, and detected the CYP2C9*3/*3 genotype. CYP2C9*3/*3 subjects metabolized much less losartan into E-3174 than CYP2C9*1/*1 subjects. [ABSTRACT FROM AUTHOR]

Glipizide is an oral hypoglycemic agent widely used to treat type 2 diabetes mellitus. In this study, an efficient HPLC-UV assay method for determining the plasma glipizide level was developed, validated, and used to assess the pharmacokinetic profile of the glipizide in healthy Korean volunteers. After extraction with diethyl ether, the chromatographic separation of glipizide was carried out using a Bondclone C18 column (10 µm, 300 × 3.9 mm) with a mobile phase of 10 mM potassium phosphate monobasic and methanol (40:60 [vol/vol], pH 3.5) and UV detection at 225 nm. The flow rate of the mobile phase was 1.0 mL/min and the retention time of glipizide and internal standard (I.S.) was approximately 11.5 and 8.6 minutes, respectively. The quantification limit was 15 ng/mL and the linear range of the calibration curve ranged from 15 to 800 ng/mL in plasma with a correlation coefficient >0.9999. The mean accuracy was 86-101%. The coefficient of variation (precision) in the intra- and inter-day validation was 1.8-14.2 and 1.7-8.1%, respectively. The pharmacokinetics of oral glipizide was evaluated after administering 5 mg to each of 13 healthy Korean subjects. The AUCinf, Cmax, Tmax, and T1/2 were 3432 ± 886 ng·h/mL, 629.0 ± 94.2 ng/mL, 2.8 ± 1.8 h, and 3.9 ± 0.9 h, respectively. The results showed large inter-individual differences in the AUCinf, Cmax and T1/2. [ABSTRACT FROM AUTHOR]

This study was aimed to validate a reliable analytical method for the pharmacokinetic study of amiloride in human plasma by a high performance liquid chromatography (HPLC) system with UV detection. Triamterene was used as an internal standard. After extraction with ethylacetate, the supernatant was evaporated. Then, the residue was reconstituted and an aliquot was injected onto the HPLC system. Separation was performed on a Capcell Pak C18 UG120 column (4.6 mm × 150 mm, 5 µm particles) with a mobile phase of 12% acetonitrile containing 0.4% glacial acetic acid and UV detection at a wavelength of 360 nm. The intra- and inter-day precision expressed as the relative standard deviation was less than 15%. The flow rate of mobile phase was 1 mL/min and the retention time of amiloride and internal standard, triamterene, was found to be 3.06 and 8.80 min, respectively. The lower limit of quantification (LOQ) was 0.2 ng/mL of amiloride using 1 mL of plasma. The calibration curve was linear in the concentration range of 0.2-50 ng/mL (r2 = 1.0000). The mean accuracy was 85.1-101.7%. The coefficient of variation (precision) in the intra- and inter-day validation was 2.1-12.5 and 2.4-13.7%, respectively. The pharmacokinetics of amiloride was evaluated after a single oral administration of 10 mg to healthy volunteers. The AUC0-72hr, Cmax, Tmax, and T1/2 were 267.7 ± 60.0 ng·hr/mL, 22.9 ± 5.4 ng/mL, 3.0 ± 0.8 hr, and 13.6 ± 2.4 hr, respectively. These results demonstrated that this method was highly feasible and reproducible for pharmacokinetic studies of amiloride in eight volunteers after oral adminis-tration (10 mg as amiloride HCl). [ABSTRACT FROM AUTHOR]

Abstract: A simple and sensitive high performance liquid chromatography method using UV detection (HPLC-UV) for the determination of meloxicam in human plasma was developed and validated. After extraction with diethyl ether, the chromatographic separation of meloxicam was carried out using a reverse phase Sunfire C18 column (150mm×4.6mm, 5μm) with a mobile phase of acetonitrile–20mM potassium hydrogen phosphate (40:60, v/v, pH 3.5) and UV detection at a wavelength of 355nm. The flow rate of mobile phase was 1.2ml/min and the retention time of meloxicam and internal standard, piroxicam, was found to be 11.6 and 6.3min, respectively. The calibration curve was linear within the concentration range, 10–2400ng/ml (r 2 >0.9999). The lower limit of quantification was 10ng/ml. This method improved the sensitivity for the quantification of meloxicam in plasma using a HPLC-UV. The mean accuracy was 98–114%. The coefficient of variation (precision) in the intra- and inter-day validation was 1.6–4.3 and 2.4–7.3%, respectively. The pharmacokinetics of meloxicam was evaluated after administering an oral dose of 15mg to 11 healthy Korean subjects. The AUCinf, C max, t max and t 1/2 were 42.4±13.2μgh/ml, 1445.7±305.5ng/ml, 4.1±0.3h and 22.0±4.9h, respectively. [Copyright &y& Elsevier]