METHODS: In 20 patients undergoing cardiac surgery in sevoflurane-remifentanil anesthesia, we analyzed intraoperative S' values which were determined after 10 min exposure to sevoflurane at 1.0, 2.0, and 3.0 inspired-vol% (T1, T2, and T3, respectively) with a fixed remifentanil dose (1.0 μg/kg/min) using transesophageal echocardiography.
RESULTS: Linear mixed-effect modeling demonstrated dose-dependent declines in S' according to the end-tidal sevoflurane concentration increments (C(ET)-sevoflurane, p < 0.001): the mean value of S' reduction for each 1.0 vol%-increment of C(ET)-sevoflurane was 1.7 cm/s (95 % confidence interval 1.4-2.1 cm/s). Medians of S' at T1, T2, and T3 (9.6, 8.9, and 7.5 cm/s, respectively) also exhibited significant declines (by 6.6, 15.6, and 21.2 % for T1 vs. T2, T2 vs. T3, and T1 vs. T3, p < 0.001, =0.002, and <0.001 in Friedman pairwise comparisons, respectively).
CONCLUSIONS: Administering sevoflurane as a part of a sevoflurane-remifentanil anesthesia regimen appears to dose-dependently reduce S', indicating LV systolic performance, in patients undergoing cardiac surgery. Further studies may be required to evaluate the clinical implications of these findings.
METHODS: Subjects (n = 121) received oral repaglinide (4 mg). Blood samples were taken at 0, 30, 60, 120, 180 and 240 min and serum concentrations of repaglinide were determined using high-performance liquid chromatography. Subjects were also genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for CYP3A4*4, *5 and*18 and by an allele-specific multiplex PCR for CYP2C8*2, *3, *4 and *5 alleles.
RESULTS: The allele frequencies of CYP2C8*1, *2, *3, *4 and *5 were 95.04, 0.40, 0.40, 0 and 4.13%, respectively. The frequencies of the CYP3A4*1, *4, *5 and *18 alleles were 97.93, 0, 0 and 2.07%, respectively. CYP2C8 and CYP3A4 genotypes were not significantly associated with repaglinide's blood glucose-lowering effect. However, the CYP3A4 genotype significantly influenced some of repaglinide's pharmacokinetics, where the mean elimination rate constant was 44.0% lower (p = 0.04) and the mean half-life was 33.8% higher (p = 0.04) in subjects with the CYP3A4*1/*18 genotype as compared to those with the normal CYP3A4*1/*1 genotype. This result confirms that CYP3A4 plays a large role in metabolizing repaglinide.
CONCLUSION: Genetic polymorphisms of CYP3A4, specifically CYP3A4*18, play a major role in contributing to the interindividual variability in repaglinide's pharmacokinetics.
METHODS: This double-blind, multicenter, phase 3 study consisted of a 1-week observation period during which patients were treated with two patches of placebo, followed by a 6-week double-blind period where patients were randomized (1:1:1) to receive once-daily blonanserin 40 mg, blonanserin 80 mg, or placebo patches. The primary endpoint was the change from baseline in the total Positive and Negative Symptom Scale (PANSS) score. Safety assessments included treatment-emergent adverse events (TEAEs).
RESULTS: Between December 2014 and October 2018, patients were recruited and randomly assigned to blonanserin 40 mg (n = 196), blonanserin 80 mg (n = 194), or placebo (n = 190); of these, 77.2% completed the study. Compared with placebo, blonanserin significantly improved PANSS total scores at 6 weeks (least square mean [LSM] difference vs placebo: -5.6 with blonanserin 40 mg; 95% confidence interval [CI] -9.6, -1.6; adjusted p = 0.007, and - 10.4 with blonanserin 80 mg; 95% CI -14.4, -6.4; adjusted p