Most children are exposed to perfluoroalkyl substances (PFASs) through placental transfer, breastfeeding, and other environmental sources. To date, there are no validated tools to estimate exposure and body burden during infancy and childhood. In this study, we aimed to (i) develop a two-generation pharmacokinetic model of prenatal and postnatal exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS), and perfluorohexanesulfonate (PFHxS); and to (ii) evaluate it against measured children's levels in two studies. We developed a pharmacokinetic model consisting of a maternal and a child compartment to simulate lifetime exposure in women and transfer to the child across the placenta and through breastfeeding. To evaluate the model, we performed simulations for each mother-child dyad from two studies in which maternal PFAS levels at delivery and children's PFAS levels were available. Model predictions based on maternal PFAS levels, sex of child, body weight, and duration of breastfeeding explained between 52% and 60% of the variability in measured children's levels at 6 months of age and between 52% and 62% at 36 months. Monte Carlo simulations showed that the daily intake through breastfeeding and resulting internal PFAS levels can be much higher in nursing infants than in mothers. This pharmacokinetic model shows potential for postnatal exposure assessment in the context of epidemiological studies and risk assessment.
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http://dx.doi.org/10.1021/acs.est.5b04399 | DOI Listing |
Clin Pharmacokinet
January 2025
Facultés de Médecine et de Pharmacie de Lyon, Univ Lyon, Université Claude Bernard Lyon 1, Lyon, France.
Background And Objective: Limited information is available on the pharmacokinetics of rifampicin (RIF) along with that of its active metabolite, 25-deacetylrifampicin (25-dRIF). This study aimed to analyse the pharmacokinetic data of RIF and 25-dRIF collected in adult patients treated for tuberculosis.
Methods: In adult patients receiving 10 mg/kg of RIF as part of a standard regimen for drug-susceptible pulmonary tuberculosis enrolled in the Opti-4TB study, plasma RIF and 25-dRIF concentrations were measured at various occasions.
Int J Biol Macromol
January 2025
School of Life Sciences, Zhengzhou University, Henan, Zhengzhou 450001, China; School of Advanced Agricultural Sciences, Peking University, Beijing 100000, China; Longhu Laboratory, Henan, Zhengzhou 450001, China; Henan Key Laboratory of Immunobiology, Henan, Zhengzhou 450001, China; College of Veterinary Medicine, Henan Agricultural University, Henan, Zhengzhou 450001, China. Electronic address:
Autoimmune diseases are characterized by dysregulated immune responses and chronic inflammation. B cell activating factor (BAFF) and interleukin-17 (IL-17) are key mediators in the pathogenesis of several autoimmune diseases, driving B cell hyperactivation, autoantibody production, and tissue damage. Simultaneous targeting of these pathways may provide a synergistic therapeutic approach.
View Article and Find Full Text PDFJ Pharm Sci
January 2025
Clinical Pharmacology, Pharmacometrics & Bioanalysis, Bristol Myers Squibb, Princeton, NJ, USA.
Iberdomide, a novel potent cereblon E3 ligase modulator, is under investigation for multiple myeloma. This study assessed how renal impairment (RI) affects iberdomide pharmacokinetics (PK). Twenty-six subjects with varying renal function, including those with severe renal impairment and those requiring intermittent hemodialysis (IHD), received a single oral 1 mg dose of iberdomide.
View Article and Find Full Text PDFAnimal Model Exp Med
January 2025
School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Background: In a previous study, we found that Atractylodes macrocephala and Paeoniae radix (AM-PR) was useful for the alleviation of functional constipation (FC). However, the precise mechanism underlying the compatibility between AM and PR in the treatment of FC remains uncertain. This study aims to analyze the pharmacokinetic differences in the active ingredients in the blood of rat models with FC when applied individually and in combination with AM-PR.
View Article and Find Full Text PDFJ Med Chem
January 2025
Center for Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610064, China.
Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths globally, and the need for effective systemic therapies for HCC is urgent. Our previous work reveals that Pin1 is a potential anti-HCC target, which regulates miRNA biogenesis and identifies as a novel Pin1 inhibitor to suppresses HCC. However, a great demand in HCC therapy as well as the limited chemical stability and pharmacokinetic feature of motivated us to find improved Pin1 inhibitors.
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