Fluoroquinolones are broad-spectrum antibiotics that accumulate in the environment. To assess human exposure through the food chain, we developed a pharmacokinetic model of fluoroquinolone accumulation in fish and a human pharmacokinetic model to predict gastrointestinal concentrations of ciprofloxacin, a common fluoroquinolone, following consumption of fish. At 70 ng/L ciprofloxacin, the average in North American surface waters, the fish steady-state concentration was calculated to be 7.5 × 10 µg/g. Upon human consumption of the FDA-recommended portion of 113 g of fish containing this ciprofloxacin level, the predicted human intestinal concentration was 2 × 10 µg/mL. At 4 × 10 ng/L (4 µg/mL) ciprofloxacin, the highest recorded environmental measurement, these numbers were 0.42 µg/g in fish and 0.1 µg/mL in the human intestine. Thus, based on the ciprofloxacin MIC for E. coli of 0.13 µg/mL, background environmental ciprofloxacin levels are unlikely to be problematic, but environmental pollution can result in high intestinal levels that may cause gut dysbiosis and antibiotic resistance.
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http://dx.doi.org/10.1016/j.etap.2023.104359 | DOI Listing |
Expert Rev Clin Pharmacol
January 2025
Department of Medical Cosmetology, Hunan Provincial Hospital of Maternal and Child Health Care.
Background: Anrikefon (HSK21542), a potent and selective peripheral kappa opioid receptor (KOR) agonist developed by Haisco, effectively blocks pain and itch signals.
Aim: To develop a population pharmacokinetic (PK) model for anrikefon and conduct exposure-response (E-R) analysis for safety and efficacy in postoperative pain patients.
Method: The Population PK analysis uses NONMEM software with data from six trials.
Nat Commun
January 2025
School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai, China.
Accidental ingestion of lead (Pb)-contaminated soils represents a major route of Pb exposure for both adults and children, and the development of accessible and cost-effective solutions to reduce Pb poisoning is urgently required. Here, we present an effective and straightforward technique, involving the consumption of cola beverages, for the purpose of lowering blood Pb levels following the ingestion of contaminated soils in animal models. This method facilitated the direct passage of Pb in contaminated soil through the digestive system, enhancing its elimination without absorption into systemic circulation.
View Article and Find Full Text PDFJ Pharmacokinet Pharmacodyn
January 2025
Department of Clinical Pharmacy and Pharmacy Administration, West China school of Pharmacy, Sichuan University, Chengdu, 610064, China.
Alogliptin is a highly selective inhibitor of dipeptidyl peptidase-4 and primarily excreted as unchanged drug in the urine, and differences in clinical outcomes in renal impairment patients increase the risk of serious adverse reactions. In this study, we developed a comprehensive physiologically-based quantitative systematic pharmacology model of the alogliptin-glucose control system to predict plasma exposure and use glucose as a clinical endpoint to prospectively understand its therapeutic outcomes with varying renal function. Our model incorporates a PBPK model for alogliptin, DPP-4 activity described by receptor occupancy theory, and the crosstalk and feedback loops for GLP-1-GIP-glucagon, insulin, and glucose.
View Article and Find Full Text PDFCancer Chemother Pharmacol
January 2025
Clinical Pharmacology & Quantitative Pharmacology, BioPharmaceuticals R&D, AstraZeneca, Waltham, MA, USA.
Purpose: Durvalumab in combination with gemcitabine/cisplatin has shown a favorable benefit-risk profile in the TOPAZ-1 study for advanced biliary tract cancers (BTC). This analysis evaluated the population pharmacokinetics (PopPK) of durvalumab, and exposure-response for efficacy and safety (ERES) of TOPAZ-1.
Methods: The PopPK model for durvalumab was updated using data from 5 previously analysed studies and TOPAZ-1.
J Antimicrob Chemother
January 2025
Service of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Rue du Bugnon 17, 1011, Lausanne, Switzerland.
Background: Model-informed precision dosing (MIPD) combines population pharmacokinetic knowledge with therapeutic drug monitoring (TDM) to optimize dosage adjustment. It could improve target concentration attainment over empirical TDM, still widely practised for broad-spectrum antibiotics.
Objectives: To evaluate the respective performance of TDM and MIPD in achieving target piperacillin exposure.
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