Spatial epidemiology is the description and analysis of geographic patterns and variations in disease risk factors,morbidity and mortality with respect to their distributions associated with demographic,socioeconomic,...Spatial epidemiology is the description and analysis of geographic patterns and variations in disease risk factors,morbidity and mortality with respect to their distributions associated with demographic,socioeconomic,environmental,health behavior,and genetic risk factors,and time-varying changes.In the Letter to Editor,we had a brief description of the practice for the mortality and the spacetime patterns of John Snow's map of cholera epidemic in London,United Kingdom in 1854.This map is one of the earliest public heath practices of developing and applying spatial epidemiology.In the early history,spatial epidemiology was predominantly applied in infectious disease and risk factor studies.However,since the recent decades,noncommunicable diseases have become the leading cause of death in both developing and developed countries,spatial epidemiology has been used in the study of noncommunicable disease.In the Letter,we addressed two examples that applied spatial epidemiology to cluster and identify stroke belt and diabetes belt across the states and counties in the United States.Similar to any other epidemiological study design and analysis approaches,spatial epidemiology has its limitations.We should keep in mind when applying spatial epidemiology in research and in public health practice.展开更多
Repaglinide is type 2 short acting anti-diabetic drug which is primarily metabolized by CYP2C8 and CYP3A4 and is also a substrate of influx transporter OATP1B1. HIV drugs are potent inhibitors of CYP3A4 and OATP trans...Repaglinide is type 2 short acting anti-diabetic drug which is primarily metabolized by CYP2C8 and CYP3A4 and is also a substrate of influx transporter OATP1B1. HIV drugs are potent inhibitors of CYP3A4 and OATP transporters. Several drug-drug interactions (DDIs) were noticed when protease inhibitors (PIs) coadministered with drugs metabolized by CYP3A4. The PIs are also potent mechanism based inhibitors, out which ritonavir is most potent. In the current study we evaluated in vitro (mouse and human liver microsomes) and in vivo DDIs of repaglinide with anti-HIV drugs. Out of the following tested drugs (Amprenavir, Indinavir, Nelfinavir, Ritonavir, Saquinavir, Delavirdine, Maraviroc, Efavirenz, Nevirapine and Ketoconazole) Amprenavir (APV), Ritonavir (RTV) and Ketoconazole (KTZ) showed inhibition of OH-repaglinide formation in human and mouse liver microsomes. The positive reversible inhibitions were further tested for irreversible inhibitions where we didn’t observe any irreversible inhibitions. In vitro inhibitions were further evaluated in the in vivo pharmacokinetics (mouse) where repaglinide pharmacokinetics was altered by RTV and KTZ. The DDIs in both studies were very strong;the dose of repaglinide is reduced to 20 fold. In conclusion, there could be possible DDIs when RTV dosed with repaglinide;we have also demonstrated that mouse could be useful preclinical tool when used in conjunction with in vitro screening models for DDIs.展开更多
文摘Spatial epidemiology is the description and analysis of geographic patterns and variations in disease risk factors,morbidity and mortality with respect to their distributions associated with demographic,socioeconomic,environmental,health behavior,and genetic risk factors,and time-varying changes.In the Letter to Editor,we had a brief description of the practice for the mortality and the spacetime patterns of John Snow's map of cholera epidemic in London,United Kingdom in 1854.This map is one of the earliest public heath practices of developing and applying spatial epidemiology.In the early history,spatial epidemiology was predominantly applied in infectious disease and risk factor studies.However,since the recent decades,noncommunicable diseases have become the leading cause of death in both developing and developed countries,spatial epidemiology has been used in the study of noncommunicable disease.In the Letter,we addressed two examples that applied spatial epidemiology to cluster and identify stroke belt and diabetes belt across the states and counties in the United States.Similar to any other epidemiological study design and analysis approaches,spatial epidemiology has its limitations.We should keep in mind when applying spatial epidemiology in research and in public health practice.
文摘Repaglinide is type 2 short acting anti-diabetic drug which is primarily metabolized by CYP2C8 and CYP3A4 and is also a substrate of influx transporter OATP1B1. HIV drugs are potent inhibitors of CYP3A4 and OATP transporters. Several drug-drug interactions (DDIs) were noticed when protease inhibitors (PIs) coadministered with drugs metabolized by CYP3A4. The PIs are also potent mechanism based inhibitors, out which ritonavir is most potent. In the current study we evaluated in vitro (mouse and human liver microsomes) and in vivo DDIs of repaglinide with anti-HIV drugs. Out of the following tested drugs (Amprenavir, Indinavir, Nelfinavir, Ritonavir, Saquinavir, Delavirdine, Maraviroc, Efavirenz, Nevirapine and Ketoconazole) Amprenavir (APV), Ritonavir (RTV) and Ketoconazole (KTZ) showed inhibition of OH-repaglinide formation in human and mouse liver microsomes. The positive reversible inhibitions were further tested for irreversible inhibitions where we didn’t observe any irreversible inhibitions. In vitro inhibitions were further evaluated in the in vivo pharmacokinetics (mouse) where repaglinide pharmacokinetics was altered by RTV and KTZ. The DDIs in both studies were very strong;the dose of repaglinide is reduced to 20 fold. In conclusion, there could be possible DDIs when RTV dosed with repaglinide;we have also demonstrated that mouse could be useful preclinical tool when used in conjunction with in vitro screening models for DDIs.
