RESUMO
The topic of joint angle and frequency estimation (JAFE) has aroused extensive interests in the past decades. Current estimation algorithms mainly rely on the Nyquist sampling criterion. In order not to cause ambiguity for parameter estimation, the space-time intervals must be smaller than given thresholds, which results in complicated hardware costs and a huge computational burden. This paper aims to reduce the complexity for JAFE, and a novel sparsity-aware framework is proposed. Unlike the current uniform sampling architectures, the incoming narrow-band singles are sampled by a series of space-time coprime samplers. An improved rotational invariance estimator is introduced, which offers closed-form solutions for both angle and frequency estimation. The mathematical treatments indicate that our methodology is inherent in larger spatial/temporal aperture than the uniform sampling architectures; hence, it provides more accurate JAFE compared to alternative approaches relying on uniform sampling. Additionally, it attains nearly the same complexity as the current rotational invariance approach. Numerical results agree with the theoretical advantages of our methodology.
RESUMO
AIM: This study examined whether gene polymorphisms (CYP3A4, ABCG2, SLCO1B1, NR1I2, PPARA and NFKB1) influenced the pharmacokinetics of lovastatin in Chinese healthy subjects. PATIENTS & METHOD: Plasma concentrations of lovastatin and lovastatin acid were quantified using LC/MS/MS. RESULTS: PPARA c.208+3819 G allele carriers had approximately twofold higher AUC0-∞ and Cmax of lovastatin than wild-type (PPARA c.208+3819 AA) subjects. After adjustment for the PPARA variants, subjects with the SLCO1B1 521TT genotype had approximately 50% lower AUC0-∞ of lovastatin acid than those with 521TC/CC genotypes, while the AUC0-∞ of lovastatin lactone in NFKB1-94 DD wild-type carriers was twofold higher than in mutant homozygotes carriers. CONCLUSION: Gene polymorphisms of PPARA, SLCO1B1 and NFKB1 affected the pharmacokinetics of lovastatin.
Assuntos
Povo Asiático/genética , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Lovastatina/farmacocinética , Polimorfismo de Nucleotídeo Único/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Citocromo P-450 CYP3A/genética , Voluntários Saudáveis , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/sangue , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Lovastatina/sangue , Subunidade p50 de NF-kappa B/genética , Proteínas de Neoplasias/genética , PPAR alfa/genética , Receptor de Pregnano X , Receptores de Esteroides/genéticaRESUMO
The nuclear receptors (NR)-farnesoid X receptor (FXR, NR1H4) and pregnane X receptor (PXR, NR1I2)-have important effects on the expression of genes related to the pharmacokinetics (PKs) of rosuvastatin. This study was designed to investigate whether the genetic variants in drug disposition genes (SLCO1B1 and ABCG2) combined with their upstream regulators (NR1H4 and NR1I2) would affect the PKs of rosuvastatin in a Chinese population. Sixty-one healthy male volunteers were enrolled and the plasma concentrations of rosuvastatin were measured using the liquid chromatographic-tandem mass spectrometry/MS method. All subjects were analyzed and grouped according to the genotypes of NR1H4, NR1I2, SLCO1B1, and ABCG2. The exposure of rosuvastatin was higher in subjects carrying the SLCO1B1 521C or ABCG2 421A allele compared with noncarriers. No association was observed of single-nucleotide polymorphisms in NR1H4 or NR1I2 genes with the PKs of rosuvastatin. After adjusting for the 421C>A and 521T>C variants, the Cmax in subjects with NR1I2 63396TT wild type were about 2-fold of those of NR1I2 mutant type (63396CC and CT) (10.7 vs. 20.4 ng/mL, P = 0.023), whereas no significant differences were observed for other parameters. Polymorphisms investigated in the genes of NR1H4 and NR1I2 seemed to play no significant role in the disposition of rosuvastatin.
Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Povo Asiático/genética , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Proteínas de Neoplasias/genética , Receptores Citoplasmáticos e Nucleares/genética , Receptores de Esteroides/genética , Rosuvastatina Cálcica/farmacocinética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Adulto , Voluntários Saudáveis , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Transportador 1 de Ânion Orgânico Específico do Fígado/metabolismo , Masculino , Proteínas de Neoplasias/metabolismo , Polimorfismo de Nucleotídeo Único/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único/genética , Receptor de Pregnano X , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores de Esteroides/metabolismo , Adulto JovemRESUMO
A rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method was developed and validated for simultaneous quantification of simvastatin (SV), its metabolite simvastatin hydroxy acid (SVA) and berberine (BBR) in rat plasma. Separation was performed on Poroshell 120 EC-C18 column (4.6×50mm, 2.7µm) using gradient elution by mobile phase containing acetonitrile and 10mM ammonium acetate (pH 4.5). Polarity switch (positive-negative-positive ionization mode) was performed in a total run time of 4.0min. The lower limits of quantification (LLOQ) for SV, SVA and BBR were 0.10, 0.20 and 0.10ng/mL, respectively. The response function was established for concentration range of 0.10-100ng/mL for SV and BBR and 0.20-3000ng/mL for SVA, with a coefficient of correlation of >0.99 for all the compounds. The proposed method was applied to the drug-drug pharmacokinetic interaction study of SV combined with BBR after oral administration in rats.
