The Use of Microdosing for In vivo Phenotyping of Cytochrome P450 Enzymes: Where Do We Stand? A Narrative Review
AbstractCytochrome P450 (CYP) enzymes play a central role in the elimination of approximately 80% of all clinically used drugs. Differences in CYP enzyme activity between individuals can contribute to interindividual variability in exposure and, therefore, treatment outcome. In vivo CYP enzyme activity could be determined with phenotyping. Currently, (sub)therapeutic doses are used for in vivo phenotyping, which can lead to side effects. The use of microdoses (100 µg) for in vivo phenotyping for CYP enzymes could overcome the limitations associated with the use of (sub)therapeutic doses of substrates. The aim of this re...
Source: European Journal of Drug Metabolism and Pharmacokinetics - April 30, 2024 Category: Drugs & Pharmacology Source Type: research
Loureirin A is a narrow-spectrum antimicrobial agent against < em > Helicobacter pylori < /em >
In this study, loureirin A (LrA), a traditional Chinese medicine monomer extracted from Sanguis Draconis flavones, was found to possess specific antibacterial activity against H. pylori without the bacteria displaying a tendency to develop resistance in vitro. LrA demonstrated a synergistic or additive effect when combined with omeprazole (a proton pump inhibitor) against H. pylori. The combination of LrA and omeprazole showed promising anti-H. pylori potential, exhibiting notable in vivo efficacy comparable to standard triple therapy in mouse models infected with both drug-sensitive and drug-resistant H. pylori strains. M...
Source: Antimicrobial Agents and Chemotherapy - April 24, 2024 Category: Microbiology Authors: Qian Tong Chengqiang Yin Xudong Hang Yuefan Bai Chongwen Zhang Jingcheng Xu Yan Huang Yixin Ge Tianyu Chen Liping Zeng Jia Jia Hongkai Bi Source Type: research
Loureirin A is a narrow-spectrum antimicrobial agent against < em > Helicobacter pylori < /em >
In this study, loureirin A (LrA), a traditional Chinese medicine monomer extracted from Sanguis Draconis flavones, was found to possess specific antibacterial activity against H. pylori without the bacteria displaying a tendency to develop resistance in vitro. LrA demonstrated a synergistic or additive effect when combined with omeprazole (a proton pump inhibitor) against H. pylori. The combination of LrA and omeprazole showed promising anti-H. pylori potential, exhibiting notable in vivo efficacy comparable to standard triple therapy in mouse models infected with both drug-sensitive and drug-resistant H. pylori strains. M...
Source: Antimicrobial Agents and Chemotherapy - April 24, 2024 Category: Microbiology Authors: Qian Tong Chengqiang Yin Xudong Hang Yuefan Bai Chongwen Zhang Jingcheng Xu Yan Huang Yixin Ge Tianyu Chen Liping Zeng Jia Jia Hongkai Bi Source Type: research
Loureirin A is a narrow-spectrum antimicrobial agent against < em > Helicobacter pylori < /em >
In this study, loureirin A (LrA), a traditional Chinese medicine monomer extracted from Sanguis Draconis flavones, was found to possess specific antibacterial activity against H. pylori without the bacteria displaying a tendency to develop resistance in vitro. LrA demonstrated a synergistic or additive effect when combined with omeprazole (a proton pump inhibitor) against H. pylori. The combination of LrA and omeprazole showed promising anti-H. pylori potential, exhibiting notable in vivo efficacy comparable to standard triple therapy in mouse models infected with both drug-sensitive and drug-resistant H. pylori strains. M...
Source: Antimicrobial Agents and Chemotherapy - April 24, 2024 Category: Microbiology Authors: Qian Tong Chengqiang Yin Xudong Hang Yuefan Bai Chongwen Zhang Jingcheng Xu Yan Huang Yixin Ge Tianyu Chen Liping Zeng Jia Jia Hongkai Bi Source Type: research
Loureirin A is a narrow-spectrum antimicrobial agent against < em > Helicobacter pylori < /em >
In this study, loureirin A (LrA), a traditional Chinese medicine monomer extracted from Sanguis Draconis flavones, was found to possess specific antibacterial activity against H. pylori without the bacteria displaying a tendency to develop resistance in vitro. LrA demonstrated a synergistic or additive effect when combined with omeprazole (a proton pump inhibitor) against H. pylori. The combination of LrA and omeprazole showed promising anti-H. pylori potential, exhibiting notable in vivo efficacy comparable to standard triple therapy in mouse models infected with both drug-sensitive and drug-resistant H. pylori strains. M...
Source: Antimicrobial Agents and Chemotherapy - April 24, 2024 Category: Microbiology Authors: Qian Tong Chengqiang Yin Xudong Hang Yuefan Bai Chongwen Zhang Jingcheng Xu Yan Huang Yixin Ge Tianyu Chen Liping Zeng Jia Jia Hongkai Bi Source Type: research
Loureirin A is a narrow-spectrum antimicrobial agent against < em > Helicobacter pylori < /em >
In this study, loureirin A (LrA), a traditional Chinese medicine monomer extracted from Sanguis Draconis flavones, was found to possess specific antibacterial activity against H. pylori without the bacteria displaying a tendency to develop resistance in vitro. LrA demonstrated a synergistic or additive effect when combined with omeprazole (a proton pump inhibitor) against H. pylori. The combination of LrA and omeprazole showed promising anti-H. pylori potential, exhibiting notable in vivo efficacy comparable to standard triple therapy in mouse models infected with both drug-sensitive and drug-resistant H. pylori strains. M...
Source: Antimicrobial Agents and Chemotherapy - April 24, 2024 Category: Microbiology Authors: Qian Tong Chengqiang Yin Xudong Hang Yuefan Bai Chongwen Zhang Jingcheng Xu Yan Huang Yixin Ge Tianyu Chen Liping Zeng Jia Jia Hongkai Bi Source Type: research
Loureirin A is a narrow-spectrum antimicrobial agent against < em > Helicobacter pylori < /em >
In this study, loureirin A (LrA), a traditional Chinese medicine monomer extracted from Sanguis Draconis flavones, was found to possess specific antibacterial activity against H. pylori without the bacteria displaying a tendency to develop resistance in vitro. LrA demonstrated a synergistic or additive effect when combined with omeprazole (a proton pump inhibitor) against H. pylori. The combination of LrA and omeprazole showed promising anti-H. pylori potential, exhibiting notable in vivo efficacy comparable to standard triple therapy in mouse models infected with both drug-sensitive and drug-resistant H. pylori strains. M...
Source: Antimicrobial Agents and Chemotherapy - April 24, 2024 Category: Microbiology Authors: Qian Tong Chengqiang Yin Xudong Hang Yuefan Bai Chongwen Zhang Jingcheng Xu Yan Huang Yixin Ge Tianyu Chen Liping Zeng Jia Jia Hongkai Bi Source Type: research
Phenotype-Genotype Correlation Applying a Cocktail Approach and an Exome Chip Analysis Reveals Further Variants Contributing to Variation of Drug Metabolism
Clin Pharmacol Ther. 2024 Apr 18. doi: 10.1002/cpt.3270. Online ahead of print.ABSTRACTAlthough great progress has been made in the fine-tuning of diplotypes, there is still a need to further improve the predictability of individual phenotypes of pharmacogenetically relevant enzymes. The aim of this study was to analyze the additional contribution of sex and variants identified by exome chip analysis to the metabolic ratio of five probe drugs. A cocktail study applying dextromethorphan, losartan, omeprazole, midazolam, and caffeine was conducted on 200 healthy volunteers. CYP2D6, 2C9, 2C19, 3A4/5, and 1A2 genotypes were an...
Source: Clinical Pharmacology and Therapeutics - April 19, 2024 Category: Drugs & Pharmacology Authors: Ruwen B öhm Henrike Bruckmueller Stefan Oswald Matthias H übenthal Meike Kaehler Lena Ehmke Jan H öcker Werner Siegmund Andre Franke Ingolf Cascorbi Source Type: research
Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence
Conclusions: Despite the well-established cancer risk associated with PPIs, it is notable that these medications continue to be widely prescribed for periods longer than 3 months. Thus, it is of paramount importance for clinicians and patients to thoughtfully evaluate the potential risks and benefits of long-term PPI usage and explore alternative treatments before making informed decisions regarding their medical management.PMID:38610738 | DOI:10.3390/jcm13071970 (Source: Clinical Colorectal Cancer)
Source: Clinical Colorectal Cancer - April 13, 2024 Category: Cancer & Oncology Authors: Ibrahim O Sawaid Abraham O Samson Source Type: research
Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence
Conclusions: Despite the well-established cancer risk associated with PPIs, it is notable that these medications continue to be widely prescribed for periods longer than 3 months. Thus, it is of paramount importance for clinicians and patients to thoughtfully evaluate the potential risks and benefits of long-term PPI usage and explore alternative treatments before making informed decisions regarding their medical management.PMID:38610738 | PMC:PMC11012754 | DOI:10.3390/jcm13071970 (Source: Clinical Colorectal Cancer)
Source: Clinical Colorectal Cancer - April 13, 2024 Category: Cancer & Oncology Authors: Ibrahim O Sawaid Abraham O Samson Source Type: research
Unusual cause of abdominal pain
Case presentation An 18-year-old woman presented with a 4-day history of worsening abdominal pain. Physical examination revealed tenderness in the left mid abdomen, without rebound tenderness. Laboratory workups revealed neutrophilia (10 890/µL), elevated C reactive protein (38.59 mg/L) and increased faecal calprotectin (>50 µg/g). Haemoglobin, liver function, renal function and urinalysis results were within normal range. Immunological investigations, including immunoglobulin levels, antineutrophil cytoplasmic antibodies and antinuclear antibodies, were all normal. An abdominal CT scan demonstrated wall thi...
Source: Gut - April 5, 2024 Category: Gastroenterology Authors: Zhang, J.-Y., Wu, T.-N., Ding, Y., Huang, W.-F. Tags: GUT Snapshot, Gut Editor ' s quiz: GI snapshot Source Type: research
The Ptk2-Pma1 pathway enhances tolerance to terbinafine in < em > Trichophyton rubrum < /em >
Antimicrob Agents Chemother. 2024 Apr 3:e0160923. doi: 10.1128/aac.01609-23. Online ahead of print.ABSTRACTThe increasing prevalence of dermatophyte resistance to terbinafine, a key drug in the treatment of dermatophytosis, represents a significant obstacle to treatment. Trichophyton rubrum is the most commonly isolated fungus in dermatophytosis. In T. rubrum, we identified TERG_07844, a gene encoding a previously uncharacterized putative protein kinase, as an ortholog of budding yeast Saccharomyces cerevisiae polyamine transport kinase 2 (Ptk2), and found that T. rubrum Ptk2 (TrPtk2) is involved in terbinafine tolerance. ...
Source: Antimicrobial Agents and Chemotherapy - April 3, 2024 Category: Microbiology Authors: Masaki Ishii Tsuyoshi Yamada Kazuki Ishikawa Koji Ichinose Michel Monod Shinya Ohata Source Type: research
Assessment of CYP-Mediated Drug Interactions for Enasidenib Based on a Cocktail Study in Patients with Relapse or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
J Clin Pharmacol. 2024 Apr 2. doi: 10.1002/jcph.2436. Online ahead of print.ABSTRACTAs a selective and potent inhibitor targeting the isocitrate dehydrogenase-2 (IDH2) mutant protein, enasidenib obtained approval from the US Food and Drug Administration (FDA) in 2017 for adult patients with acute myeloid leukemia (AML) with an IDH2 mutation. In vitro investigations demonstrated that enasidenib affects various drug metabolic enzymes and transporters. This current investigation aimed to assess enasidenib on the pharmacokinetics (PKs) of CYP substrates, including dextromethorphan (CYP2D6 probe drug), flurbiprofen (CYP2C9 prob...
Source: The Journal of Clinical Pharmacology - April 2, 2024 Category: Drugs & Pharmacology Authors: Yiming Cheng Xiaomin Wang Atalanta Ghosh Jie Pu Leonidas N Carayannopoulos Yan Li Source Type: research
Assessment of CYP-Mediated Drug Interactions for Enasidenib Based on a Cocktail Study in Patients with Relapse or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
J Clin Pharmacol. 2024 Apr 2. doi: 10.1002/jcph.2436. Online ahead of print.ABSTRACTAs a selective and potent inhibitor targeting the isocitrate dehydrogenase-2 (IDH2) mutant protein, enasidenib obtained approval from the US Food and Drug Administration (FDA) in 2017 for adult patients with acute myeloid leukemia (AML) with an IDH2 mutation. In vitro investigations demonstrated that enasidenib affects various drug metabolic enzymes and transporters. This current investigation aimed to assess enasidenib on the pharmacokinetics (PKs) of CYP substrates, including dextromethorphan (CYP2D6 probe drug), flurbiprofen (CYP2C9 prob...
Source: The Journal of Clinical Pharmacology - April 2, 2024 Category: Drugs & Pharmacology Authors: Yiming Cheng Xiaomin Wang Atalanta Ghosh Jie Pu Leonidas N Carayannopoulos Yan Li Source Type: research
