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In recent years, the coamorphous drug delivery system has been established as a promising formulation approach for delivering poorly water-soluble drugs. The coamorphous solid is a single-phase system containing an active pharmaceutical ingredient (API) and other low molecular weight molecules that might be pharmacologically relevant APIs or excipients. These formulations exhibit considerable advantages over neat crystalline or amorphous material, including improved physical stability, dissolution profiles, and potentially enhanced therapeutic efficacy. This review provides a comprehensive overview of coamorphous drug delivery systems from the perspectives of preparation, physicochemical characteristics, physical stability, and performance. Furthermore, the challenges and strategies in developing robust coamorphous drug products of high quality and performance are briefly discussed.
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Objective: To evaluate the effects of CYP2C19 genetic polymorphism on the plasma concentration of voriconazole in patients with hematological disease and the value of serial monitoring plasma concentrations in the treatment and prevention of invasive fungal disease (IFD). Methods: From January 2016 to December 2016, 65 hematological patients who received voriconazole intravenous administration for the treatment of invasive fungal disease were enrolled in this study. The population CYP2C19 polymorphism of voriconazole were performed using PCR-Pyrosequencing. The trough plasma concentrations of vriconazole (Ctrough) was detected by ultra performance liquid chromatography tandem mass spectrometry. Results: Based on the genotype analysis, 65 subjects were identified as extensive metabolizers' group (30 cases) and poor metabolizers' group (35 cases). The Ctrough of the 65 patients were detected for 169 times totally, and there was a significant difference of Ctrough values between the two groups [0.98(0.38-2.08) mg/L vs 2.19(1.53-4.27) mg/L, z=10.286, P<0.001]. The medium of Ctrough in 65 hematological patients were described. Lack of response to therapy was more frequent in patients with voriconazole levels <1.5 mg/L (50.0%) than in those with voriconazole levels >1.5 mg/L (20.5%) (P=0.052). And the risk of adverse events was more frequent in patients with voriconazole levels >5.5 mg/L (80.0%) than in those with voriconazole levels ≤5.5 mg/L (8.3%) (χ2=11.689, P=0.020). Conclusion: Patients with CYP2C19 wild-type phenotype are extensive metabolizers, their Ctrough of voriconazole are significantly lower than patients with CYP2C19 non-wild-type phenotype (poor metabolizers). Appropriate concentrations of vriconazole can improve the efficacy and safety during treatment.
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Humanos , Antifúngicos , Citocromo P-450 CYP2C19/genética , Genotipo , Enfermedades Hematológicas/genética , Micosis , Fenotipo , Polimorfismo Genético , VoriconazolRESUMEN
Objective@#To evaluate the effects of CYP2C19 genetic polymorphism on the plasma concentration of voriconazole in patients with hematological disease and the value of serial monitoring plasma concentrations in the treatment and prevention of invasive fungal disease (IFD).@*Methods@#From January 2016 to December 2016, 65 hematological patients who received voriconazole intravenous administration for the treatment of invasive fungal disease were enrolled in this study. The population CYP2C19 polymorphism of voriconazole were performed using PCR-Pyrosequencing. The trough plasma concentrations of vriconazole (Ctrough) was detected by ultra performance liquid chromatography tandem mass spectrometry.@*Results@#Based on the genotype analysis, 65 subjects were identified as extensive metabolizers’ group (30 cases) and poor metabolizers’ group (35 cases). The Ctrough of the 65 patients were detected for 169 times totally, and there was a significant difference of Ctrough values between the two groups [0.98(0.38-2.08) mg/L vs 2.19(1.53-4.27) mg/L, z=10.286, P<0.001]. The medium of Ctrough in 65 hematological patients were described. Lack of response to therapy was more frequent in patients with voriconazole levels <1.5 mg/L (50.0%) than in those with voriconazole levels >1.5 mg/L (20.5%) (P=0.052). And the risk of adverse events was more frequent in patients with voriconazole levels >5.5 mg/L (80.0%) than in those with voriconazole levels ≤5.5 mg/L (8.3%) (χ2=11.689, P=0.020).@*Conclusion@#Patients with CYP2C19 wild-type phenotype are extensive metabolizers, their Ctrough of voriconazole are significantly lower than patients with CYP2C19 non-wild-type phenotype (poor metabolizers). Appropriate concentrations of vriconazole can improve the efficacy and safety during treatment.
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OBJECTIVE: To develop an ultra-high performance liquid chromatography-mass spectrometry method for the determination of glimepiride and its metabolites (M1) simultaneously in human plasma.
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OBJECTIVE: To analyze the correlation between UPLC-MS/MS method and HPLC-UV method for determination of mycophenolic acid (MPA) blood concentrations in renal transplant patients and to establish a generally applicable conversion method of the determination results. METHODS: MPA concentrations in whole blood and plasma of transplant patients were determined by UPLC-MS/MS method. Plasma concentrations of MPA were determined by HPLC-UV. Variance analysis of the measure results was done by LEVENE and LSD methods, and the correlation between the methods was analyzed by Spearman method. RESULTS: Three conversion formula were obtained as follows; YUPLC_MS/MS plasma)=1.612 XUPLD_MS/M/Swhole blood+0.686, YUPLC_MS/MS plasma=1.414XUPLD_MS/M/S whole blood-0.206, and YHPLC-LV plasam=0.848 XUPLD_MS/M/S whole blood-0.692. CONCLUSION: There is good correlation between UPLC-MS/MS method and HPLC-UV method for the determination of MPA concentration in whole blood and plasma in renal transplant patients. The results can be transformed by equations.
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OBJECTIVE:To reference clinical utilization of amikacin of a hospital.METHODS:By retrospective survey,the clinical information of 30 inpatients who were treated with amikacin and received plasma concentration monitoring from Apr.2006 to Feb.2010 were analyzed statistically in respect of primary disease,results of pathogen culture and drug sensitivity test,dosages and usage,plasma concentration,clinical efficacy,adverse drug reactions,etc.RESULTS:Clinical response rate was 55.2% and dosage of amikacin was small as well as measured value and reference value of plasma concentration.No adverse drug reaction was observed.CONCLUSION:The proportion of amikacin should be increased and plasma concentration monitoring of amikacin should be strengthened.Individual regimen is realized to improve effectiveness and safety of drug use.
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60 years old). 43 cases of antiepileptic drugs combination accounted for 10% and the therapeutic plasma concentration of 27 cases deviated from normal range(62.8%). CONCLUSION:Results of plasma concentration monitoring provide an important basis for clinical drug use. Monitoring data and other clinical index can promote rational use of antiepileptic drugs.
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In Therapeutic Drug Monitoring (TDM), does and intervals of administration are adjusted according to the individual patient based on plasma concentrations predicted from one or two measurements of the patient. Such monitoring has been applied to many kinds of drugs and is necessary in the study of Kampo formulations too. In this kind of monitoring, the selection of measurement points is quite important in order to achieve accurate predictions. The purpose of this paper is to propose a Monte Carlo approach to the selection of the optimum measurement point to predict plasma concentrations of a drug. The proposed approach is applied to the data obtained in a clinical phase-one study of a Kampo formulation. The necessity of Therapeutic Drug Monitoring for Kampo formulations is also discussed.