ABSTRACT
Background: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has resulted in acute respiratory distress, fatal systemic manifestations (extrapulmonary as well as pulmonary), and premature mortality among many patients. Therapy for COVID-19 has focused on the treatment of symptoms and of acute inflammation (cytokine storm) and the prevention of viral infection. Although the mechanism of COVID-19 is not fully understood, potential clinical targets have been identified for pharmacological, immunological, and vaccinal approaches. Area covered: Pharmacological approaches including drug repositioning have been a priority for initial COVID-19 therapy due to the time-consuming nature of the vaccine development process. COVID-19 drugs have been shown to manage the antiviral infection cycle (cell entry and replication of proteins and genomic RNA) and anti-inflammation. In this review, we evaluated the interaction of current COVID-19 drugs with two ATP-binding cassette transporters [P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP)] and potential drug-drug interactions (DDIs) among COVID-19 drugs, especially those associated with P-gp and BCRP efflux transporters. Expert opinion: Overall, understanding the pharmacodynamic/pharmacokinetic DDIs of COVID-19 drugs can be useful for pharmacological therapy in COVID-19 patients.
ABSTRACT
Background The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has resulted in acute respiratory distress, fatal systemic manifestations (extrapulmonary as well as pulmonary), and premature mortality among many patients. Therapy for COVID-19 has focused on the treatment of symptoms and of acute inflammation (cytokine storm) and the prevention of viral infection. Although the mechanism of COVID-19 is not fully understood, potential clinical targets have been identified for pharmacological, immunological, and vaccinal approaches. Area covered Pharmacological approaches including drug repositioning have been a priority for initial COVID-19 therapy due to the time-consuming nature of the vaccine development process. COVID-19 drugs have been shown to manage the antiviral infection cycle (cell entry and replication of proteins and genomic RNA) and anti-inflammation. In this review, we evaluated the interaction of current COVID-19 drugs with two ATP-binding cassette transporters [P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP)] and potential drug-drug interactions (DDIs) among COVID-19 drugs, especially those associated with P-gp and BCRP efflux transporters. Expert opinion Overall, understanding the pharmacodynamic/pharmacokinetic DDIs of COVID-19 drugs can be useful for pharmacological therapy in COVID-19 patients.
ABSTRACT
A high-performance liquid chromatography-ultraviolet detector (HPLC-UV) method has been used to quantify teicoplanin concentrations in human plasma. However, the limited analytical accuracy of previously bioanalytical methods for teicoplanin has given rise to uncertainty due to the use of an external standard. In this study, an internal standard (IS), polymyxin B, was applied to devise a precise, accurate, and feasible HPLC-UV method. The deproteinized plasma sample containing teicoplanin and an IS of acetonitrile was chromatographed on a C18 column with an acidic mobile phase consisting of NaH2PO4 buffer and acetonitrile (78:22, v/v) by isocratic elution and detection at 220 nm. The linearity was in the range 7.8-500 mg/L calculated by the ratio of the teicoplanin signal to the IS signal. This analytical method, validated by FDA guidelines with ICH Q2 (R1), was successfully applied to analyze the plasma samples of patients in the intensive care unit for treating serious resistant bacterial infectious diseases, such as those by methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. The methods suggested the potential for use in routine clinical practice for therapeutic drug monitoring of teicoplanin, providing both improved accuracy and a wide range of linearity from lower than steady-state trough concentrations (10 mg/L) to much higher concentrations.