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Chimpanzees are genetically and physiologically similar to humans. Several pharmacokinetic models of propofol are available and target controlled infusion (TCI) of propofol is established in humans, but not in chimpanzees. The purpose of this study was to investigate if human pharmacokinetic models can accurately predict propofol plasma concentration (Cp) in chimpanzees and if it is feasible to perform TCI in chimpanzees. Ten chimpanzees were anaesthetized for regular veterinary examinations. Propofol was used as an induction or maintenance agent. Blood samples were collected from a catheter in a cephalic vein at 3-7 time points between 1 and 100 min following the propofol bolus and/or infusion in five chimpanzees, or TCI in six chimpanzees. Cp was measured using high-performance liquid chromatography. The Marsh, Schnider and Eleveld human pharmacokinetic models were used to predict Cp for each case and we examined the predictive performances of these models using the Varvel criteria Median PE and Median APE. Median PE and Median APE for Marsh, Schnider and Eleveld models were within or close to the acceptable range. A human TCI pump was successfully maintained propofol Cp during general anesthesia in six chimpanzees. Human propofol pharmacokinetic models and TCI pumps can be applied in chimpanzees.
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http://dx.doi.org/10.1038/s41598-020-79914-7 | DOI Listing |
Microb Drug Resist
September 2025
Drug Discovery Research, Wockhardt Research Centre, Wockhardt Ltd., Chhatrapati Sambhajinagar, India.
Cefepime (FEP), a fourth-generation cephalosporin combined with tazobactam (TAZ), a β-lactamase inhibitor, is being developed by Wockhardt as a pharmacodynamically optimized fixed dose combination (FEP-2 g + TAZ-2 g) for the treatment of multidrug-resistant Gram-negative infections. To undertake an exposure-response analysis for establishing pharmacokinetic (PK)/pharmacodynamic (PD) targets, it is crucial to characterize the PK profile of compounds in surrogate compartments, such as plasma and lung, in clinically relevant animal infection models used to evaluate efficacy. In the current study, PKs of FEP and TAZ were assessed in plasma and in epithelial lining fluid (ELF) of neutropenic noninfected, lung-infected, and thigh-infected mice.
View Article and Find Full Text PDFJ Med Chem
September 2025
Guangzhou National Laboratory, Guangzhou 510005, P. R. China.
Respiratory syncytial virus (RSV) is a major pathogen causing acute respiratory infections, and the RSV fusion glycoprotein (F) has been identified as a key target for developing small-molecule inhibitors. Based on our prior identification of lonafarnib as an F protein inhibitor, medicinal chemistry efforts led to the development of , which exhibits significantly enhanced potency against both laboratory and clinical RSV isolates in cellular assays. Time-of-addition and SPR assays indicate that inhibits viral entry by targeting the RSV F protein, but has farnesyltransferase-independent antiviral efficacy.
View Article and Find Full Text PDFProteomics Clin Appl
September 2025
Institute of Biochemistry, Center for Preventive Doping Research, German Sport University Cologne, Cologne, Germany.
Purpose: Hormonal contraceptives are linked to a higher prevalence of depressive symptoms. Given their popularity in Western countries, understanding the biochemical effects on neuronal cells is crucial to minimizing mental health risks.
Experimental Design: Neural progenitor cells were treated with ethinyl estradiol (EE) and levonorgestrel (LNG), two synthetic sex hormones commonly used in oral contraception, and S-23, a selective androgen receptor modulator developed as a potential synthetic sex hormone for male hormonal contraception.
Biomed Chromatogr
October 2025
Department of Pharmaceutical Analysis, Pharmacy School, Shenyang Pharmaceutical University, Shenyang, China.
A rapid and specific liquid chromatography-tandem mass spectrometry method with a wide linear range was developed and validated for the simultaneous quantification of Vitamin K1 (VK1) trans- and cis- isomers in human plasma. Bovine serum albumin solution (15%) served as a surrogate matrix for preparing the calibrators to establish the quantitative curves. After liquid-liquid extraction, VK1 trans- and cis- isomers in plasma samples were separated on a ChromCore C30 column (15 cm × 4.
View Article and Find Full Text PDFPharm Res
September 2025
Axcelead Tokyo West Partners, Inc. Translational Science, Discovery DMPK, Hino-Shi, Tokyo, 191-0065, Japan.
Purpose: Accurate prediction of human clearance (CL) is essential in early drug development. Single Species Scaling (SSS) using rat pharmacokinetic (PK) data, particularly with unbound plasma fraction (f), is widely used. However, its accuracy declines for compounds with extremely low f, and no systematic method has addressed this limitation.
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