Danazol increases the oral bioavailability of midazolam by inactivation of hepatic and intestinal CYP3A in rats
In this study, we investigated the effects of DNZ on CYP3A activity in hepatic and small intestinal microsomes and the pharmacokinetics of midazolam (MDZ), a typical substrate for CYP3A, in rats.MDZ 4-hydroxylation activities in hepatic and small intestinal microsomes significantly decreased 24 h after DNZ (100 mg/kg, i.p.) treatment. Time-dependent inactivation of MDZ 4-hydroxylation activities was noted when microsomes were pre-incubated with DNZ in the presence of a NADPH-generating system.The Western blot analysis indicated that the decrease observed in enzyme activity was not due to changes in the protein expression o...
Source: Xenobiotica - August 28, 2023 Category: Research Authors: Shuhei Fukuno Katsuhito Nagai Akemi Kurotobi Yuki Sahori Ryo Nakagawa Rena Nomura Takuya Ito Hiroki Konishi Source Type: research
Danazol increases the oral bioavailability of midazolam by inactivation of hepatic and intestinal CYP3A in rats
In this study, we investigated the effects of DNZ on CYP3A activity in hepatic and small intestinal microsomes and the pharmacokinetics of midazolam (MDZ), a typical substrate for CYP3A, in rats.2. MDZ 4-hydroxylation activities in hepatic and small intestinal microsomes significantly decreased 24 hours after DNZ (100 mg/kg, i.p.) treatment. Time-dependent inactivation of MDZ 4-hydroxylation activities was noted when microsomes were pre-incubated with DNZ in the presence of a NADPH-generating system.3. The Western blot analysis indicated that the decrease observed in enzyme activity was not due to changes in the protein ex...
Source: Xenobiotica - August 28, 2023 Category: Research Authors: Shuhei Fukuno Katsuhito Nagai Akemi Kurotobi Yuki Sahori Ryo Nakagawa Rena Nomura Takuya Ito Hiroki Konishi Source Type: research
Danazol increases the oral bioavailability of midazolam by inactivation of hepatic and intestinal CYP3A in rats
In this study, we investigated the effects of DNZ on CYP3A activity in hepatic and small intestinal microsomes and the pharmacokinetics of midazolam (MDZ), a typical substrate for CYP3A, in rats.2. MDZ 4-hydroxylation activities in hepatic and small intestinal microsomes significantly decreased 24 hours after DNZ (100 mg/kg, i.p.) treatment. Time-dependent inactivation of MDZ 4-hydroxylation activities was noted when microsomes were pre-incubated with DNZ in the presence of a NADPH-generating system.3. The Western blot analysis indicated that the decrease observed in enzyme activity was not due to changes in the protein ex...
Source: Xenobiotica - August 28, 2023 Category: Research Authors: Shuhei Fukuno Katsuhito Nagai Akemi Kurotobi Yuki Sahori Ryo Nakagawa Rena Nomura Takuya Ito Hiroki Konishi Source Type: research
Danazol increases the oral bioavailability of midazolam by inactivation of hepatic and intestinal CYP3A in rats
In this study, we investigated the effects of DNZ on CYP3A activity in hepatic and small intestinal microsomes and the pharmacokinetics of midazolam (MDZ), a typical substrate for CYP3A, in rats.2. MDZ 4-hydroxylation activities in hepatic and small intestinal microsomes significantly decreased 24 hours after DNZ (100 mg/kg, i.p.) treatment. Time-dependent inactivation of MDZ 4-hydroxylation activities was noted when microsomes were pre-incubated with DNZ in the presence of a NADPH-generating system.3. The Western blot analysis indicated that the decrease observed in enzyme activity was not due to changes in the protein ex...
Source: Xenobiotica - August 28, 2023 Category: Research Authors: Shuhei Fukuno Katsuhito Nagai Akemi Kurotobi Yuki Sahori Ryo Nakagawa Rena Nomura Takuya Ito Hiroki Konishi Source Type: research
Danazol increases the oral bioavailability of midazolam by inactivation of hepatic and intestinal CYP3A in rats
In this study, we investigated the effects of DNZ on CYP3A activity in hepatic and small intestinal microsomes and the pharmacokinetics of midazolam (MDZ), a typical substrate for CYP3A, in rats.2. MDZ 4-hydroxylation activities in hepatic and small intestinal microsomes significantly decreased 24 hours after DNZ (100 mg/kg, i.p.) treatment. Time-dependent inactivation of MDZ 4-hydroxylation activities was noted when microsomes were pre-incubated with DNZ in the presence of a NADPH-generating system.3. The Western blot analysis indicated that the decrease observed in enzyme activity was not due to changes in the protein ex...
Source: Xenobiotica - August 28, 2023 Category: Research Authors: Shuhei Fukuno Katsuhito Nagai Akemi Kurotobi Yuki Sahori Ryo Nakagawa Rena Nomura Takuya Ito Hiroki Konishi Source Type: research
Danazol increases the oral bioavailability of midazolam by inactivation of hepatic and intestinal CYP3A in rats
In this study, we investigated the effects of DNZ on CYP3A activity in hepatic and small intestinal microsomes and the pharmacokinetics of midazolam (MDZ), a typical substrate for CYP3A, in rats.2. MDZ 4-hydroxylation activities in hepatic and small intestinal microsomes significantly decreased 24 hours after DNZ (100 mg/kg, i.p.) treatment. Time-dependent inactivation of MDZ 4-hydroxylation activities was noted when microsomes were pre-incubated with DNZ in the presence of a NADPH-generating system.3. The Western blot analysis indicated that the decrease observed in enzyme activity was not due to changes in the protein ex...
Source: Xenobiotica - August 28, 2023 Category: Research Authors: Shuhei Fukuno Katsuhito Nagai Akemi Kurotobi Yuki Sahori Ryo Nakagawa Rena Nomura Takuya Ito Hiroki Konishi Source Type: research
Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions for Encorafenib. Part I. Model Building, Validation and Prospective Predictions with Enzyme Inhibitors, Inducers and Transporter Inhibitors
Xenobiotica. 2023 Aug 23:1-42. doi: 10.1080/00498254.2023.2250856. Online ahead of print.ABSTRACTEncorafenib, a potent BRAF kinase inhibitor undergoes significant metabolism by CYP3A4 (83%) and CYP2C19 (16%) and also a substrate of P-glycoprotein (P-gp). Because of this, encorafenib possesses potential for enzyme-transporter related interactions. Clinically, it's drug-drug interactions (DDI) with CYP3A4 inhibitors (posaconazole, diltiazem) were reported and hence there is a necessity to study DDI's with multiple enzyme inhibitors, inducers and P-gp inhibitors.USFDA recommended clinical CYP3A4, CYP2C19, P-gp inhibitors, CYP...
Source: Xenobiotica - August 23, 2023 Category: Research Authors: Sivacharan Kollipara Tausif Ahmed Sivadasu Praveen Source Type: research
Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions for Encorafenib. Part I. Model Building, Validation and Prospective Predictions with Enzyme Inhibitors, Inducers and Transporter Inhibitors
Xenobiotica. 2023 Aug 23:1-42. doi: 10.1080/00498254.2023.2250856. Online ahead of print.ABSTRACTEncorafenib, a potent BRAF kinase inhibitor undergoes significant metabolism by CYP3A4 (83%) and CYP2C19 (16%) and also a substrate of P-glycoprotein (P-gp). Because of this, encorafenib possesses potential for enzyme-transporter related interactions. Clinically, it's drug-drug interactions (DDI) with CYP3A4 inhibitors (posaconazole, diltiazem) were reported and hence there is a necessity to study DDI's with multiple enzyme inhibitors, inducers and P-gp inhibitors.USFDA recommended clinical CYP3A4, CYP2C19, P-gp inhibitors, CYP...
Source: Xenobiotica - August 23, 2023 Category: Research Authors: Sivacharan Kollipara Tausif Ahmed Sivadasu Praveen Source Type: research
Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions for Encorafenib. Part I. Model Building, Validation and Prospective Predictions with Enzyme Inhibitors, Inducers and Transporter Inhibitors
Xenobiotica. 2023 Aug 23:1-42. doi: 10.1080/00498254.2023.2250856. Online ahead of print.ABSTRACTEncorafenib, a potent BRAF kinase inhibitor undergoes significant metabolism by CYP3A4 (83%) and CYP2C19 (16%) and also a substrate of P-glycoprotein (P-gp). Because of this, encorafenib possesses potential for enzyme-transporter related interactions. Clinically, it's drug-drug interactions (DDI) with CYP3A4 inhibitors (posaconazole, diltiazem) were reported and hence there is a necessity to study DDI's with multiple enzyme inhibitors, inducers and P-gp inhibitors.USFDA recommended clinical CYP3A4, CYP2C19, P-gp inhibitors, CYP...
Source: Xenobiotica - August 23, 2023 Category: Research Authors: Sivacharan Kollipara Tausif Ahmed Sivadasu Praveen Source Type: research
Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions for Encorafenib. Part I. Model Building, Validation and Prospective Predictions with Enzyme Inhibitors, Inducers and Transporter Inhibitors
Xenobiotica. 2023 Aug 23:1-42. doi: 10.1080/00498254.2023.2250856. Online ahead of print.ABSTRACTEncorafenib, a potent BRAF kinase inhibitor undergoes significant metabolism by CYP3A4 (83%) and CYP2C19 (16%) and also a substrate of P-glycoprotein (P-gp). Because of this, encorafenib possesses potential for enzyme-transporter related interactions. Clinically, it's drug-drug interactions (DDI) with CYP3A4 inhibitors (posaconazole, diltiazem) were reported and hence there is a necessity to study DDI's with multiple enzyme inhibitors, inducers and P-gp inhibitors.USFDA recommended clinical CYP3A4, CYP2C19, P-gp inhibitors, CYP...
Source: Xenobiotica - August 23, 2023 Category: Research Authors: Sivacharan Kollipara Tausif Ahmed Sivadasu Praveen Source Type: research
Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions for Encorafenib. Part I. Model Building, Validation and Prospective Predictions with Enzyme Inhibitors, Inducers and Transporter Inhibitors
Xenobiotica. 2023 Aug 23:1-42. doi: 10.1080/00498254.2023.2250856. Online ahead of print.ABSTRACTEncorafenib, a potent BRAF kinase inhibitor undergoes significant metabolism by CYP3A4 (83%) and CYP2C19 (16%) and also a substrate of P-glycoprotein (P-gp). Because of this, encorafenib possesses potential for enzyme-transporter related interactions. Clinically, it's drug-drug interactions (DDI) with CYP3A4 inhibitors (posaconazole, diltiazem) were reported and hence there is a necessity to study DDI's with multiple enzyme inhibitors, inducers and P-gp inhibitors.USFDA recommended clinical CYP3A4, CYP2C19, P-gp inhibitors, CYP...
Source: Xenobiotica - August 23, 2023 Category: Research Authors: Sivacharan Kollipara Tausif Ahmed Sivadasu Praveen Source Type: research
Metabolic exhaustion and casein kinase 1 α drive deguelin-induced premature red blood cell death
Xenobiotica. 2023 Aug 21:1-9. doi: 10.1080/00498254.2023.2248492. Online ahead of print.ABSTRACT1. Deguelin (DGN), a retinoid isolated from many plants, exhibits a potent anticancer activity against a wide spectrum of tumour cells. There is a dearth of evidence, however, regarding the toxicity of DGN to red blood cells (RBCs). This is relevant given the prevalent chemotherapy-associated anaemia observed in cancer patients.2. RBCs were exposed to 1-100 μM of DGN for 24 h at 37 °C. Haemolysis and related markers were photometrically measured while flow cytometry was employed to detect phosphatidylserine exposure through An...
Source: Xenobiotica - August 17, 2023 Category: Research Authors: Mohammad A Alfhili Jawaher Alsughayyir Source Type: research
Metabolic exhaustion and casein kinase 1 α drive deguelin-induced premature red blood cell death
Xenobiotica. 2023 Aug 21:1-9. doi: 10.1080/00498254.2023.2248492. Online ahead of print.ABSTRACT1. Deguelin (DGN), a retinoid isolated from many plants, exhibits a potent anticancer activity against a wide spectrum of tumour cells. There is a dearth of evidence, however, regarding the toxicity of DGN to red blood cells (RBCs). This is relevant given the prevalent chemotherapy-associated anaemia observed in cancer patients.2. RBCs were exposed to 1-100 μM of DGN for 24 h at 37 °C. Haemolysis and related markers were photometrically measured while flow cytometry was employed to detect phosphatidylserine exposure through An...
Source: Xenobiotica - August 17, 2023 Category: Research Authors: Mohammad A Alfhili Jawaher Alsughayyir Source Type: research
Metabolic exhaustion and casein kinase 1 α drive deguelin-induced premature red blood cell death
Xenobiotica. 2023 Aug 17:1-11. doi: 10.1080/00498254.2023.2248492. Online ahead of print.ABSTRACT1. Deguelin (DGN), a retinoid isolated from many plants, exhibits a potent anticancer activity against a wide spectrum of tumour cells. There is a dearth of evidence, however, regarding the toxicity of DGN to red blood cells (RBCs). This is relevant given the prevalent chemotherapy-associated anaemia observed in cancer patients.2. RBCs were exposed to 1-100 μM of DGN for 24 h at 37 °C. Haemolysis and related markers were photometrically measured while flow cytometry was employed to detect phosphatidylserine exposure through A...
Source: Xenobiotica - August 17, 2023 Category: Research Authors: Mohammad A Alfhili Jawaher Alsughayyir Source Type: research
Metabolic exhaustion and casein kinase 1 α drive deguelin-induced premature red blood cell death
Xenobiotica. 2023 Aug 17:1-11. doi: 10.1080/00498254.2023.2248492. Online ahead of print.ABSTRACT1. Deguelin (DGN), a retinoid isolated from many plants, exhibits a potent anticancer activity against a wide spectrum of tumour cells. There is a dearth of evidence, however, regarding the toxicity of DGN to red blood cells (RBCs). This is relevant given the prevalent chemotherapy-associated anaemia observed in cancer patients.2. RBCs were exposed to 1-100 μM of DGN for 24 h at 37 °C. Haemolysis and related markers were photometrically measured while flow cytometry was employed to detect phosphatidylserine exposure through A...
Source: Xenobiotica - August 17, 2023 Category: Research Authors: Mohammad A Alfhili Jawaher Alsughayyir Source Type: research
