Article
Medicine, Research & Experimental
Theodore Decaix, Romain Magny, Isabelle Gouin-Thibaut, Xavier Delavenne, Patrick Mismetti, Joe-Elie Salem, Celine Narjoz, Anne Blanchard, Marion Pepin, Nicolas Auzeil, Marie-Anne Loriot, Olivier Laprevote
Summary: This study found that the levels of certain ceramides and phosphatidylcholines in the blood were associated with ABCB1 genotype and clarithromycin intake. The results highlight the relevance of untargeted lipidomics for studying in vivo P-gp activity and safely phenotyping transporters.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Anesthesiology
Terhi J. Lohela, Satu Poikola, Mikko Neuvonen, Mikko Niemi, Janne T. Backman, Klaus T. Olkkola, Tuomas O. Lilius
Summary: Rifampin significantly reduces the concentrations of oral and intravenous hydromorphone by enhancing its first-pass and systemic metabolism, likely involving the induction of glucuronosyltransferase enzymes.
ANESTHESIA AND ANALGESIA
(2021)
Article
Infectious Diseases
Beatrix Wulkersdorfer, Sebastian G. Wicha, Elizaveta Kurdina, Stephan F. Carrion Carrera, Peter Matzneller, Valentin Al Jalali, Matthias G. Vossen, Sonja Riesenhuber, Edith Lackner, Christoph Dorn, Markus Zeitlinger
Summary: This study investigated the protein binding of an anti-infective drug in vitro and in vivo using clindamycin. Concentration-dependent protein binding was observed with slightly lower levels of unbound drug fractions in vitro compared to in vivo.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Mahdi Ghadi, Seyed Jalal Hosseinimehr, Fereshteh Talebpour Amiri, Alireza Mardanshahi, Zohreh Noaparast
Summary: P-glycoprotein (P-gp) serves as a vital efflux pump in chemotherapy resistance in human colon cancer. The study demonstrates the synergistic anti-tumor activity of itraconazole and paclitaxel, showing enhanced cytotoxicity and tumor growth suppression. Additionally, Tc-99m-MIBI is identified as an effective radiotracer for monitoring response to treatment in MDR tumors.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Ruchika Bajaj, Lisa B. Chong, Ling Zou, Eleftheria Tsakalozou, Zhanglin Ni, Kathleen M. Giacomini, Deanna L. Kroetz
Summary: P-glycoprotein (P-gp) is crucial for drug oral bioavailability, and inhibiting its function can enhance drug absorption. A study found that most oral molecular excipients do not affect P-gp transport, providing a wide selection of excipients for oral formulations with minimal risk of impacting the bioavailability of P-gp substrate drugs.
Article
Pharmacology & Pharmacy
Jurgen Scheuenpflug, Dirk Kropeit, Katharina Erb-Zohar, Jochen G. W. Theis, Hans-Peter Stobernack, David McCormick, Holger Zimmermann, Helga Ruebsamen-Schaeff
Summary: Letermovir, a human CMV terminase inhibitor, was investigated for its potential to alter the pharmacokinetics of digoxin in healthy subjects. The study found that concomitant administration of letermovir with digoxin resulted in a decrease in digoxin exposure, but with no clinically relevant effect on safety or tolerability.
CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT
(2022)
Article
Pharmacology & Pharmacy
Donna S. Cox, Muhammad Rehman, Tahira Khan, Katherine Ginman, Joanne Salageanu, Robert R. LaBadie, Katty Wan, Bharat Damle
Summary: This study aimed to evaluate the pharmacokinetics (PK) and safety of coadministration of nirmatrelvir/ritonavir or ritonavir alone with midazolam and dabigatran, two commonly used drugs. The results showed that coadministration with nirmatrelvir /ritonavir or ritonavir alone significantly increased the exposure of midazolam and dabigatran. However, the exposure of midazolam was comparable between nirmatrelvir/ritonavir and ritonavir alone, suggesting that nirmatrelvir had no additional effect. The slightly higher dabigatran exposure when coadministered with nirmatrelvir/ritonavir compared to ritonavir alone indicated a minor incremental effect of nirmatrelvir.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Lea Darnaud, Clement Delage, Youssef Daali, Anne-Priscille Trouvin, Serge Perrot, Nihel Khoudour, Nadia Merise, Laurence Labat, Bruno Etain, Frank Bellivier, Celia Lloret-Linares, Vanessa Bloch, Emmanuel Curis, Xavier Decleves
Summary: Drug-metabolizing enzymes and drug transporters play crucial roles in drug pharmacokinetics and response. The cocktail-based phenotyping approach involves administering multiple probe drugs to evaluate the activities of CYP and transporter simultaneously. This study determined the range of phenotyping indices in healthy volunteers and classified patients with therapeutic issues based on CYP and P-gp activities.
Article
Pharmacology & Pharmacy
Meng Fu, Lin Luo, Sheng Feng, Hongda Lin, Zekun Lu, Fei Gu, Yang Fan, Bing Wu, Jianying Huang, Kai Shen
Summary: This study evaluated the effects of SHR0302 on the pharmacokinetics of cytochrome P450 (CYP) probe substrates. The results demonstrated that co-administration of SHR0302 did not have a clinically meaningful effect on the exposure of drugs metabolized by CYP3A4, CYP2C8, CYP2C9 and CYP2C19 in healthy subjects.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Shanshan Nie, Kaifeng Chen, Chengxian Guo, Qi Pei, Chan Zou, Liangyuan Yao, Hongbo Yuan, Xia Zhao, Ran Xie, Xu He, Jie Huang, Guoping Yang
Summary: This study reveals the impact of CYP4F2 rs2074900 SNP on ticagrelor pharmacokinetics (PK) and provides new insights into the pharmacogenetics of ticagrelor.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Food Science & Technology
Yajing Fang, Fuqiang Liang, Mengmeng Xia, Weiwei Cao, Siyi Pan, Ting Wu, Xiaoyun Xu
Summary: This study found that certain flavonoids can effectively reverse multidrug resistance mediated by P-glycoprotein (P-gp) by inhibiting its activity, with specific structural groups and substitutions playing a crucial role in their inhibitory effects. Additionally, flavonoids can impact P-gp ATPase activity and expression levels, thereby influencing its drug transport activity.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Pharmacology & Pharmacy
Yingying Zhao, Zhimin Miao, Mingzhao Jiang, Xuan Zhou, Yong Lai
Summary: The study found that pretreatment with BRE did not significantly affect the pharmacokinetics of FEX, showing no significant differences in pharmacokinetic parameters and bioequivalence between the BRE and placebo-treated groups. Additionally, MDR1 C3435T gene polymorphisms also did not impact the pharmacokinetics of FEX in healthy volunteers.
Article
Chemistry, Medicinal
Yesong Shin, Chungam Choi, Eun Sil Oh, Choon Ok Kim, Kyungsoo Park, Min Soo Park
Summary: The study showed that rifampicin significantly reduced the AUC0-96h of Evogliptin without affecting Cmax. Rifampicin was found to reduce Evogliptin metabolism by inducing cytochrome P450. Co-administration of the two drugs did not significantly alter adverse events.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
Article
Medicine, Research & Experimental
Laust Moesgaard, Peter Reinholdt, Carsten Uhd Nielsen, Jacob Kongsted
Summary: Considerable effort has been devoted to the search for modulators of membrane transport proteins. This study focuses on the inhibitory effect of polysorbate 20 (PS20) on P-glycoprotein (P-gp) and aims to understand the underlying molecular mechanism. Molecular dynamics simulations revealed that the hydrophobic nature of PS20 drives its binding to the drug-binding domain of P-gp, resulting in the inhibition of the protein's function.
MOLECULAR PHARMACEUTICS
(2022)
Article
Pharmacology & Pharmacy
Kuljeet Singh, Szabolcs Tarapcsak, Zsuzsanna Gyoengy, Zsuzsanna Ritter, Gyula Batta, Rosevalentine Bosire, Judit Remenyik, Katalin Goda
Summary: P-glycoprotein (Pgp) is an important transporter protein involved in drug absorption, metabolism, and excretion, and its overexpression in cancer cells leads to drug resistance. Some polyphenols from sour cherry origin have been shown to inhibit Pgp activity and increase drug accumulation in positive cells, while others increase Pgp activity with weaker effects on drug accumulation. These polyphenols can potentially interact with Pgp and influence drug resistance in cancer cells.