- Antibiotics-induced depletion of rat microbiota induces changes in the expression of host drug-processing genes and pharmacokinetic behaviors of CYPs probe drugs. [Journal Article]Drug Metab Dispos. 2023 Jan 09 [Online ahead of print]DM
- The metabolism of exogenous substances is affected by the gut microbiota, and the relationship between them has become a hot topic. However, the mechanisms by which the microbiota regulates drug metabolism have not been clearly defined. This study characterizes the expression profiles of host drug-processing genes (DPGs) in antibiotics-treated rats by using an unbias quantitative RNA-Seq method a…
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- [Effect of Laportea bulbifera extract on CYP450 enzyme activities in rats by Cocktail probe drug method]. [Journal Article]Zhongguo Zhong Yao Za Zhi. 2022 Dec; 47(23):6320-6332.ZZ
- The Cocktail probe drug method was used to evaluate the effect of Laportea bulbifera extract on the different subtypes of CYP450 enzyme activities in rats, and to provide references for its clinical rational drug use. The rats were randomly divided into a high-dose L. bulbifera group(0.45 g·kg~(-1)·d~(-1)) and a low-dose L. bulbifera group(0.09 g·kg~(-1)·d~(-1)). After continuous gavage for 7 and…
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- Determination of CYP450 activities in diabetes mellitus rats by a UHPLC-MS/MS method. [Journal Article]J Pharm Biomed Anal. 2023 Feb 05; 224:115191.JP
- In this study, we investigated the effect of type 1 diabetes mellitus on the modulation of the activities of CYP450s in dynamics by a UHPLC-MS/MS method. The diabetic rat model was constructed by an intraperitoneal single injection of streptozotocin. Fasting blood glucose levels > 16.7 mmol/L were considered as diabetic. The rats were given a cocktail of four probe drugs (10 mg/kg phenacetin, 1 m…
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- Quantification of Paeoniflorin by Fully Validated LC-MS/MS Method: Its Application to Pharmacokinetic Interaction between Paeoniflorin and Verapamil. [Journal Article]
- A rapid, sensitive, and specific LC-MS/MS method was developed and fully validated for the detection of paeoniflorin only in rat plasma, and applied to pharmacokinetic studies, including intravenous, multi-dose oral and combined administrations with verapamil. In this study, tolbutamide was used as the internal standard, and the protein precipitation extraction method, using acetonitrile as the e…
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- Antidiabetic Actions of Ethanol Extract of Camellia sinensis Leaf Ameliorates Insulin Secretion, Inhibits the DPP-IV Enzyme, Improves Glucose Tolerance, and Increases Active GLP-1 (7-36) Levels in High-Fat-Diet-Fed Rats. [Journal Article]
- Camellia sinensis (green tea) is used in traditional medicine to treat a wide range of ailments. In the present study, the insulin-releasing and glucose-lowering effects of the ethanol extract of Camellia sinensis (EECS), along with molecular mechanism/s of action, were investigated in vitro and in vivo. The insulin secretion was measured using clonal pancreatic BRIN BD11 β cells, and mouse islet…
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- A Rapid and Sensitive LC-MS/MS Method for the Quantitation of Physalin A with Special Consideration to Chemical Stability in Rat Plasma: Application to a Pharmacokinetic Study. [Journal Article]
- Physalin A is a promising natural product with excellent anti-inflammatory and anti-tumor activities. However, the pharmacokinetic profile of physalin A is still unclear. In this study, a rapid and sensitive analytical method based on LC-MS/MS for the quantitation of physalin A in rat plasma with special consideration to its chemical stability was developed and validated. To avoid the degradation…
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- Pharmacokinetic Interactions of a Licorice Dietary Supplement with Cytochrome P450 Enzymes in Female Participants. [Journal Article]Drug Metab Dispos. 2023 Feb; 51(2):199-204.DM
- Licorice, the roots and rhizomes of Glycyrrhiza glabra L., has been used as a medicinal herb, herbal adjuvant, and flavoring agent since ancient times. Recently, licorice extracts have become popular as dietary supplements used by females to alleviate menopausal symptoms. Exposure to licorice products containing high levels of glycyrrhizic acid can cause hypokalemia, but independent from this eff…
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- Cisapride induced hypoglycemia via the KCNH6 potassium channel. [Journal Article]
- Mutations in KCNH6 has been proved to cause hypoinsulinemia and diabetes in human and mice. Cisapride is a stomach-intestinal motility drug used to treat gastrointestinal dysfunction. Cisapride has been reported to be a potential inhibitor of the KCNH family, but it remained unclear whether cisapride inhibited KCNH6. Here, we discovered the role of cisapride on glucose metabolism, focusing on the…
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- Polyphenol-Rich Leaf of Annona squamosa Stimulates Insulin Release from BRIN-BD11 Cells and Isolated Mouse Islets, Reduces (CH2O)n Digestion and Absorption, and Improves Glucose Tolerance and GLP-1 (7-36) Levels in High-Fat-Fed Rats. [Journal Article]
- Annona squamosa, commonly known as custard apple, is traditionally used for the treatment of various diseases including diabetes, cardiovascular disease (CVD), and gastritis. This study was undertaken to investigate the effects of an ethanolic (80% v/v) extract of A. squamosa (EEAS) leaves in vitro on insulin secretion from clonal pancreatic BRIN BD11 β-cells and mouse islets, including mechanist…
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- Loss of tetraspanin-7 expression reduces pancreatic β-cell exocytosis Ca2+ sensitivity but has limited effect on systemic metabolism. [Journal Article]
- CONCLUSIONS: Tspan7 is involved in the regulation of Ca2+ -dependent exocytosis in β-cells. Its function is more significant in human β-cells than their rodent counterparts.
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- Metabolite profiling analysis of hepatitis B virus-induced liver cirrhosis patients with minimal hepatic encephalopathy using gas chromatography-time-of-flight mass spectrometry and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. [Journal Article]Biomed Chromatogr. 2023 Jan; 37(1):e5529.BC
- This study used gas chromatography-time-of-flight mass spectrometry (GC-TOFMS) and ultra-performance liquid chromatography-quadrupole TOFMS (UPLC-QTOFMS) metabonomic analytical techniques in combination with bioinformatics and pattern recognition analysis methods to analyze the serum metabolite profiling of hepatitis B virus (HBV)-induced liver cirrhosis patients with minimal hepatic encephalopat…
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- Evaluation of vatiquinone drug-drug interaction potential in vitro and in a phase 1 clinical study with tolbutamide, a CYP2C9 substrate, and omeprazole, a CYP2C19 substrate, in healthy subjects. [Clinical Trial, Phase I]
- CONCLUSIONS: The in vitro and clinical studies demonstrated vatiquinone has a low potential to affect the pharmacokinetics of concomitantly administered medications that are metabolized by CYP enzymes.
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- Implications of Coexistent Halogen and Hydrogen Bonds in Amorphous Solid Dispersions on Drug Solubility, Miscibility, and Mobility. [Journal Article]Mol Pharm. 2022 11 07; 19(11):3959-3972.MP
- Specific noncovalent drug-polymer interactions were analytically identified using Raman and Fourier transform infrared spectroscopy for amorphous solid dispersions (ASD) formed between either chlorpropamide or tolbutamide and polyvinylpyrrolidone vinyl acetate random copolymer (PVPVA). Spectral changes in the C-Cl stretching vibrations due to changes in the electronic environment of the Cl atom c…
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- Insulin Secretory Actions of Ethanol Extract of Eucalyptus citriodora Leaf, including Plasma DPP-IV and GLP-1 Levels in High-Fat-Fed Rats, as Well as Characterization of Biologically Effective Phytoconstituents. [Journal Article]
- Due to the numerous adverse effects of synthetic drugs, researchers are currently studying traditional medicinal plants to find alternatives for diabetes treatment. Eucalyptus citriodora is known to be used as a remedy for various illnesses, including diabetes. This study aimed to explore the effects of ethanol extract of Eucalyptus citriodora (EEEC) on in vitro and in vivo systems, including the…
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- Evaluation of Safety and Clinically Relevant Drug-Drug Interactions with Tucatinib in Healthy Volunteers. [Journal Article]
- CONCLUSIONS: The potential DDIs identified here may be mitigated by avoiding concomitant use of tucatinib with strong CYP3A inducers, moderate CYP2C8 inducers, CYP3A substrates with a narrow therapeutic window (modifying substrate dose where concomitant use is unavoidable), and strong CYP2C8 inhibitors (decreasing tucatinib dose where concomitant use is unavoidable), or by reducing the dose of P-glycoprotein substrates with a narrow therapeutic window.
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- Evaluation of the effects of four types of tea on the activity of cytochrome P450 enzymes with a probe cocktail and HPLC-MS/MS. [Journal Article]
- CONCLUSIONS: The method used in the present study was successfully applied to assess the inhibitory effects of aqueous extracts of four types of tea on CYP450 isoforms in vitro. The results suggest that different types of tea have different effects on drug metabolism.
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- Construction of polysaccharide scaffold-based perfusion bioreactor supporting liver cell aggregates for drug screening. [Journal Article]J Biomater Sci Polym Ed. 2022 12; 33(17):2249-2269.JB
- Rebuilding a suitable microenvironment of liver cells is the key challenge to enhancing the expression of hepatic functions for drug screening in vitro. To improve the microenvironment by providing the specific adhesive ligands for hepatocytes in the three-dimensional dynamic culture, a perfusion bioreactor with a pectin/alginate blend porous scaffold was constructed in this study. The galactosyl…
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- Inhibition of imrecoxib on mRNA and protein expression of CYP2C11 enzyme in rats. [Journal Article]Biomed Chromatogr. 2022 Oct; 36(10):e5439.BC
- To evaluate the effect of imrecoxib on CYP2C11 enzyme activity, mRNA, and protein expression, a UPLC method was established. Tolbutamide was selected as the CYP2C11 enzyme-specific probe drug and incubated with imrecoxib in rat liver microsomes. The yield of 4-hydroxytolbutamide was measured using UPLC to investigate the effect of imrecoxib on CYP2C11 enzyme activity. Imrecoxib (10 mg/kg) was adm…
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- Gut microbiota and host Cyp450s co-contribute to pharmacokinetic variability in mice with non-alcoholic steatohepatitis: Effects vary from drug to drug. [Journal Article]
- CONCLUSIONS: Gut microbiota and host Cyp450s co-contribute to the pharmacokinetic variability in mice with NASH, and the degree of contribution varies from drug to drug. The present findings provide new insights into the explanation of pharmacokinetic variability in disease states.
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- Intracellular Binding of Terfenadine Competes with Its Access to Pancreatic β-cell ATP-Sensitive K+ Channels and Human ether-à-go-go-Related Gene Channels. [Journal Article]
- Most blockers of both hERG (human ether-à-go-go-related gene) channels and pancreatic β-cell ATP-sensitive K+ (KATP) channels access their binding sites from the cytoplasmic side of the plasma membrane. It is unknown whether binding to intracellular components competes with binding of these substances to K+ channels. The whole-cell configuration of the patch-clamp technique, a laser-scanning conf…
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- Development of a new LC-MS/MS method for the simultaneous identification and quantification of 13 antidiabetic drugs in human hair. [Journal Article]J Chromatogr B Analyt Technol Biomed Life Sci. 2022 Aug 01; 1205:123335.JC
- Oral antidiabetics are the drugs used to control blood sugar in diabetic subjects. The greatest risk of using these drugs is hypoglycaemia, which can be fatal if managed inappropriately. The diagnosis of hypoglycemia may be simple in diabetic subjects but can become a challenge in subjects with no history of exposure to these drugs. The major interest of testing for these compounds in hair is in …
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- Beneficial herb-drug interaction of Gnaphalium affine extract on benzbromarone: A pharmacokinetic and pharmacodynamic study in rats. [Journal Article]Phytomedicine. 2022 Jul 20; 102:154203.P
- CONCLUSIONS: PD synergism demonstrated with the BBR+GAD combination could be explained by the PK interaction observed partially from CYP2C11(9)-mediation and enterohepatic recycling.
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- Application of Physiologically Based Pharmacokinetic Modeling in Preclinical Studies: A Feasible Strategy to Practice the Principles of 3Rs. [Journal Article]
- Pharmacokinetic characterization plays a vital role in drug discovery and development. Although involving numerous laboratory animals with error-prone, labor-intensive, and time-consuming procedures, pharmacokinetic profiling is still irreplaceable in preclinical studies. With physiologically based pharmacokinetic (PBPK) modeling, the in vivo profiles of drug absorption, distribution, metabolism,…
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- Tanshinone IIA down-regulates -transforming growth factor beta 1 to relieve renal tubular epithelial cell inflammation and pyroptosis caused by high glucose. [Journal Article]
- Diabetic nephropathy (DN) is a microvascular disease caused by diabetes. Tanshinone IIA has been indicated to ameliorate streptozotocin-induced DN. This study explores the effect of tanshinone IIA on high glucose-induced renal tubular epithelial cell pyroptosis and inflammation. High glucose-stimulated HK-2 cells were used as the in-vitro model of DN and were treated with tanshinone IIA at concen…
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- Similarities in Calcium Oscillations Between Neonatal Mouse Islets and Mature Islets Exposed to Chronic Hyperglycemia. [Journal Article]
- Pulsatility is important to islet function. As islets mature into fully developed insulin-secreting micro-organs, their ability to produce oscillatory intracellular calcium ([Ca2+]i) patterns in response to glucose also matures. In this study, we measured [Ca2+]i using fluorescence imaging to characterize oscillations from neonatal mice on postnatal (PN) days 0, 4, and 12 in comparison to adult i…
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- Crystal structure of 4-bromo-N-(propyl-carbamo-yl)benzene-sulfonamide. [Journal Article]
- The title compound, C10H13BrN2O3S, 1, contains a sulfonyl urea moiety, which possesses potential therapeutic functions (e.g., anti-diabetic and herbicidal). The geometry of 1 is similar to its closely related analogues, chlorpropamide and tolbutamide. This compound crystallizes in the monoclinic space group C2/c, having one mol-ecule in its asymmetric unit. The crystal structure of 1, recorded at…
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- Glucose inhibits glucagon secretion by decreasing [Ca2+]c and by reducing the efficacy of Ca2+ on exocytosis via somatostatin-dependent and independent mechanisms. [Journal Article]
- CONCLUSIONS: We propose a model according to which glucose controls α-cell [Ca2+]c and glucagon secretion through multiple mechanisms. Increasing the glucose concentration modestly decreases [Ca2+]c in α-cells independently of their KATP channels and partly via SST. The involvement of SST increases with the glucose concentration, and one major effect of SST is to keep α-cell [Ca2+]c at low levels by counteracting the effect of an entrainment of α-cells by β-cells when β-cells become stimulated by glucose. All these [Ca2+]c changes induce parallel changes in glucagon release. Glucose also decreases the efficacy of Ca2+ on exocytosis by an attenuating pathway that is opposite to the well-established amplifying pathway controlling insulin release in β-cells.
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- Evaluation of a six-probe cocktail (caffeine, tolbutamide, omeprazole, dextromethorphan, midazolam, and digoxin) approach to estimate hepatic drug detoxification capability and dosage requirements after a single oral dosing in healthy Chinese volunteers. [Clinical Trial, Phase I]
- The primary objectives of this study were to investigate the suitability of a 6-probe cocktail (caffeine, tolbutamide, omeprazole, dextromethorphan, midazolam, and digoxin) to be used as a tool for assessing the activity of drug metabolizing enzymes and transporters, and examine differences in the way drugs are handled among groups with different genetic regulation of these processes. This was a …
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- Solids Turn into Liquids-Liquid Eutectic Systems of Pharmaceutics to Improve Drug Solubility. [Journal Article]
- The low solubility of active pharmaceutical ingredients (APIs) is a problem in pharmaceutical development. Several methodologies can be used to improve API solubility, including the use of eutectic systems in which one of the constituents is the API. This class of compounds is commonly called Therapeutic Deep Eutectic Systems (THEDES). THEDES has been gaining attention due to their properties suc…
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- Quantitation of Diclofenac, Tolbutamide, and Warfarin as Typical CYP2C9 Substrates in Rat Plasma by UPLC-MS/MS and Its Application to Evaluate Linderane-Mediated Herb-Drug Interactions. [Journal Article]
- Linderane (LDR), the main active and distinctive component of L. aggregate, is a mechanism-based inactivator of CYP2C9 in vitro, indicating the occurrence of herb-drug interactions. However, little is known about the changes of the pharmacokinetic properties of the common clinical drugs as CYP2C9 substrates after coadministration with LDR. In this study, a selective and rapid ultraperformance liq…
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