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Effect Of Epigallocatechin Gallate on Pharmacokinetics of NADOLOL In Healthy Volunteers
Posters Conclusions: The hypertensive patients with genotype TT marked the highest efficiency of amlodipine on the background of the least amount arising ADR.
Dried Blood Spot: Utilizing Dry Blood For Pharmacokinetic Investigations— An Old Method with Great Future for Therapeutic Drug Monitoring V. Maksimović 1; S. Goločorbin-Kon1; J. Cvejić Hogervorst1; H. Al-Salami2; and M. Mikov1 1 Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia; and 2Curtin Health Innovation Research Institute, Curtin University, Perth WA, Australia Background: Although dried blood (DBS), biological sampling of the full blood, was described for the first time in 1913, it found wider use in 1960s, after it was used by Robert Guthrie in 1963 for sampling of the whole blood in order to develop neonatal screening for phenylketonuria. Methods: Various techniques have been used for DBS sample analysis including liquid chromatography with mass spectrometry and liquid chromatography with tandem mass spectrometry with acceptable sensitivity, selectivity and speed. Some of the studies that used DBS included Norwegian Breast Cancer Screening Program study conducted on 3263 women who provided their DBS samples, patients admitted to Hospital del Mar in Barcelona due to intoxication with psychoactive substances, pharmacokinetic studies and therapeutic drug monitoring of antiepileptic drugs, and showed that this is a minimally invasive, cost-effective, patient-friendly technique that provides plausible results and is convenient for use in newborns and small children. Additional validations are needed in order to fully optimize this technique for use in different areas. Very important use of DBS could be in determining methotrexate metabolites in order to monitor adherence to methotrexate therapy, such as juvenile idiopathic arthritis and juvenile dermatomyositis therapy in children. A validated liquid chromatography with tandem mass spectrometry method was developed for the determination of methotrexate and methotrexate polyglutamates in Caco-2 cells exposed to methotrexate. Results: There are certain insufficiencies, such as hematocrit influence. Studies have been conducted with aim to found solutions for correcting or minimalizing its effect on the analysis and have shown promising results. Conclusions: Using optimised sample preparation and analysis, DBS technique has significant potential applications in preclinical and clinical trials, therapeutic and toxicological drug and poison monitoring, and large epidemiological trials. DBS represents a cost-effect model of drug analysis and can provide much needed pharmacokinetic results in an efficient and robust manner.
Identification and Functional Characterization of Genetic Variations in SHP-2 E.Y. Kwon; B.M. Kim; and J.H. Choi Ewha Womans University, Seoul, Republic of Korea Background: Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) is ubiquitously expressed in mammalian tissues, and dysregulation of its expression or function is implicated in the pathogenesis of various human diseases. A recent study reported that a nonsynonymous variation in SHP-2 is associated with neurodevelopment in patients with Noonan syndrome. The present study identified and functionally characterized genetic variations in SHP-2 in preterm infants and evaluated the effect of each variation on neurodevelopment in these infants. Methods: Genetic variations in SHP-2 were identified by directly sequencing or genotyping its promoter or coding regions by using DNA
August 2017
samples obtained from 72 Korean preterm infants. Each variation was functionally characterized by performing various in vitro assays such as dual-luciferase assay, gel-shift assay, and immunoblotting. Results: Eleven genetic variations were identified in this study. Of these, two variations were present in the SHP-2 promoter and one was a nonsynonymous variation. The two variations in the SHP-2 promoter significantly increased its activity compared with that of the wild-type SHP-2 promoter. However, the nonsynonymous variation did not affect SHP-2 expression. In addition, we found that the two variations in the SHP-2 promoter regulated the transcription of SHP-2 by using two transcription factors. Conclusions: Our results suggest that the two variations in the SHP2 promoter regulate its transcription rate. Another study examining the effect of these functional variations on neurodevelopment in preterm infants is ongoing.
Effect Of Epigallocatechin Gallate on Pharmacokinetics of NADOLOL In Healthy Volunteers O. Abe1; S. Misaka1; H. Sato2; H. Ogata1; T. Ono1; Y. Shikama1; S. Onoue2; H. Yabe1; and J. Kimura1 1 Fukushima Medical University School of Medicine, Fukushima, Japan; and 2University of Shizuoka School of Pharmaceutical Sciences, Shizuoka, Japan Background: Green tea is known to have beneficial effects on health, and catechins, its flavonoid components, have been reported to contribute mainly to the effects. We showed previously that continuous ingestion of green tea for 2 weeks greatly reduced plasma concentrations of nadolol, a β -blocker, in healthy volunteers. It is known that epigallocatechin gallate (EGCG) is the most abundant catechin in green tea. In this study, we examined effects of EGCG on pharmacokinetics of nadolol. Methods: A randomized open 3 phase crossover study was conducted in 13 healthy volunteers. After overnight fasting, subjects were administered nadolol 30 mg with water, EGCG 50 mg or EGCG 150 mg. A commercial green tea extract (Sunphenon EGCG, total catechin 97.4%, EGCG 92.5%) was used as EGCG by dissolving in water before administration. Blood and urine were collected up to 48 hours after administration. Results: The area under the plasma nadolol concentration-time curve (AUC) decreased by 25% and 35% (P< 0.01), maximum concentration of nadolol (Cmax) decreased by 41% (P< 0.01) and 45% (P< 0.01), respectively with EGCG 50 mg and 150 mg. The reduction of nadolol AUC with EGCG was greater with higher nadolol AUC with water. The cumulative urinary excretion of nadolol was also resulted in a significant decrease in EGCG groups without significant difference in the renal clearance of nadolol. Cmax of plasma EGCG were 52 and 108 ng/mL, respectively, in case of EGCG 50 mg and 150 mg. There was no significant difference in blood pressure and pulse in all groups. Conclusions: Our data suggest that EGCG contributes to the pharmacokinetic interaction between green tea and nadolol in healthy volunteers.
Drugs - Induced Disseminated Intravascular Coagulation: A Pharmacoepidemiological Study Based on Who Database of Adverse Drug Reactions G. Bonaldo1; L. Rossi1; L. Gasperoni1; M. Melis1,2; S. Grandi1; A. Vaccheri1; and D. Motola1 1 University of Bologna, via Irnerio 48, 40126, Bologna, Italy; and 2 Emilia-Romagna Region, Via Aldo Moro 21, 40127, Bologna, Italy
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Dried Blood Spot: Utilizing Dry Blood For Pharmacokinetic Investigations— An Old Method with Great Future for Therapeutic Drug Monitoring V. Maksimović 1; S. Goločorbin-Kon1; J. Cvejić Hogervorst1; H. Al-Salami2; and M. Mikov1 1 Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia; and 2Curtin Health Innovation Research Institute, Curtin University, Perth WA, Australia Background: Although dried blood (DBS), biological sampling of the full blood, was described for the first time in 1913, it found wider use in 1960s, after it was used by Robert Guthrie in 1963 for sampling of the whole blood in order to develop neonatal screening for phenylketonuria. Methods: Various techniques have been used for DBS sample analysis including liquid chromatography with mass spectrometry and liquid chromatography with tandem mass spectrometry with acceptable sensitivity, selectivity and speed. Some of the studies that used DBS included Norwegian Breast Cancer Screening Program study conducted on 3263 women who provided their DBS samples, patients admitted to Hospital del Mar in Barcelona due to intoxication with psychoactive substances, pharmacokinetic studies and therapeutic drug monitoring of antiepileptic drugs, and showed that this is a minimally invasive, cost-effective, patient-friendly technique that provides plausible results and is convenient for use in newborns and small children. Additional validations are needed in order to fully optimize this technique for use in different areas. Very important use of DBS could be in determining methotrexate metabolites in order to monitor adherence to methotrexate therapy, such as juvenile idiopathic arthritis and juvenile dermatomyositis therapy in children. A validated liquid chromatography with tandem mass spectrometry method was developed for the determination of methotrexate and methotrexate polyglutamates in Caco-2 cells exposed to methotrexate. Results: There are certain insufficiencies, such as hematocrit influence. Studies have been conducted with aim to found solutions for correcting or minimalizing its effect on the analysis and have shown promising results. Conclusions: Using optimised sample preparation and analysis, DBS technique has significant potential applications in preclinical and clinical trials, therapeutic and toxicological drug and poison monitoring, and large epidemiological trials. DBS represents a cost-effect model of drug analysis and can provide much needed pharmacokinetic results in an efficient and robust manner.
Identification and Functional Characterization of Genetic Variations in SHP-2 E.Y. Kwon; B.M. Kim; and J.H. Choi Ewha Womans University, Seoul, Republic of Korea Background: Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) is ubiquitously expressed in mammalian tissues, and dysregulation of its expression or function is implicated in the pathogenesis of various human diseases. A recent study reported that a nonsynonymous variation in SHP-2 is associated with neurodevelopment in patients with Noonan syndrome. The present study identified and functionally characterized genetic variations in SHP-2 in preterm infants and evaluated the effect of each variation on neurodevelopment in these infants. Methods: Genetic variations in SHP-2 were identified by directly sequencing or genotyping its promoter or coding regions by using DNA
August 2017
samples obtained from 72 Korean preterm infants. Each variation was functionally characterized by performing various in vitro assays such as dual-luciferase assay, gel-shift assay, and immunoblotting. Results: Eleven genetic variations were identified in this study. Of these, two variations were present in the SHP-2 promoter and one was a nonsynonymous variation. The two variations in the SHP-2 promoter significantly increased its activity compared with that of the wild-type SHP-2 promoter. However, the nonsynonymous variation did not affect SHP-2 expression. In addition, we found that the two variations in the SHP-2 promoter regulated the transcription of SHP-2 by using two transcription factors. Conclusions: Our results suggest that the two variations in the SHP2 promoter regulate its transcription rate. Another study examining the effect of these functional variations on neurodevelopment in preterm infants is ongoing.
Effect Of Epigallocatechin Gallate on Pharmacokinetics of NADOLOL In Healthy Volunteers O. Abe1; S. Misaka1; H. Sato2; H. Ogata1; T. Ono1; Y. Shikama1; S. Onoue2; H. Yabe1; and J. Kimura1 1 Fukushima Medical University School of Medicine, Fukushima, Japan; and 2University of Shizuoka School of Pharmaceutical Sciences, Shizuoka, Japan Background: Green tea is known to have beneficial effects on health, and catechins, its flavonoid components, have been reported to contribute mainly to the effects. We showed previously that continuous ingestion of green tea for 2 weeks greatly reduced plasma concentrations of nadolol, a β -blocker, in healthy volunteers. It is known that epigallocatechin gallate (EGCG) is the most abundant catechin in green tea. In this study, we examined effects of EGCG on pharmacokinetics of nadolol. Methods: A randomized open 3 phase crossover study was conducted in 13 healthy volunteers. After overnight fasting, subjects were administered nadolol 30 mg with water, EGCG 50 mg or EGCG 150 mg. A commercial green tea extract (Sunphenon EGCG, total catechin 97.4%, EGCG 92.5%) was used as EGCG by dissolving in water before administration. Blood and urine were collected up to 48 hours after administration. Results: The area under the plasma nadolol concentration-time curve (AUC) decreased by 25% and 35% (P< 0.01), maximum concentration of nadolol (Cmax) decreased by 41% (P< 0.01) and 45% (P< 0.01), respectively with EGCG 50 mg and 150 mg. The reduction of nadolol AUC with EGCG was greater with higher nadolol AUC with water. The cumulative urinary excretion of nadolol was also resulted in a significant decrease in EGCG groups without significant difference in the renal clearance of nadolol. Cmax of plasma EGCG were 52 and 108 ng/mL, respectively, in case of EGCG 50 mg and 150 mg. There was no significant difference in blood pressure and pulse in all groups. Conclusions: Our data suggest that EGCG contributes to the pharmacokinetic interaction between green tea and nadolol in healthy volunteers.
Drugs - Induced Disseminated Intravascular Coagulation: A Pharmacoepidemiological Study Based on Who Database of Adverse Drug Reactions G. Bonaldo1; L. Rossi1; L. Gasperoni1; M. Melis1,2; S. Grandi1; A. Vaccheri1; and D. Motola1 1 University of Bologna, via Irnerio 48, 40126, Bologna, Italy; and 2 Emilia-Romagna Region, Via Aldo Moro 21, 40127, Bologna, Italy
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