Medication use during pregnancy poses risks to both the mother and the fetus. These risks include an elevated potential for fetotoxicity due to placental drug transport. Nanomedicines offer a promising solution by potentially preventing trans-placental passage.
View Article and Find Full Text PDFBackground: Antenatal betamethasone and dexamethasone are prescribed to women who are at high risk of premature birth to prevent neonatal respiratory distress syndrome (RDS). The current treatment regimens, effective to prevent neonatal RDS, may be suboptimal. Recently, concerns have been raised regarding possible adverse long-term neurological outcomes due to high fetal drug exposures.
View Article and Find Full Text PDFTofacitinib is a small molecule Janus kinase (JAK) inhibitor, introduced to the European market in 2017, for the treatment of rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. In the treatment of women with autoimmune diseases, pregnancy is a relevant issue, as such diseases typically affect women in their reproductive years. Currently, there is limited data on the use of tofacitinib during pregnancy.
View Article and Find Full Text PDFLinezolid is used off-label for treatment of central nervous system infections. However, its pharmacokinetics and target attainment in cranial cerebrospinal fluid (CSF) in tuberculous meningitis patients is unknown. This study aimed to predict linezolid cranial CSF concentrations and assess attainment of pharmacodynamic (PD) thresholds (AUC:MIC of >119) in plasma and cranial CSF of adults and children with tuberculous meningitis.
View Article and Find Full Text PDFCommercially available physiologically-based pharmacokinetic (PBPK) modeling platforms increasingly allow estimations of fetal exposure to xenobiotics. We aimed to explore a physiology-based approach in which literature data from ex vivo placenta perfusion studies are used to parameterize Simcyp's pregnancy-PBPK (p-PBPK) model, taking crizotinib as an example. First, a physiologically-based semi-mechanistic placenta (PBMP) model was developed in MATLAB to analyze placenta perfusion data of crizotinib.
View Article and Find Full Text PDFIntroduction: To allow the continued participation of women enrolled in pre-licensure clinical trials who become pregnant, and to potentially enrol pregnant women in clinical trials, non-clinical developmental and reproductive toxicology studies (DART) are essential. Generally during pharmaceutical development, DART studies are conducted late during clinical development, leading to the exclusion of pregnant women from enrolment and withdrawal of women becoming pregnant during pre-licensure trials.
Discussion: Completing all DART studies prior to or early during the conduct of phase 3 trials (i.
Pharmaceutical residues are released in the aquatic environment due to incomplete removal from wastewater. With the presence of multiple chemicals in sewage waters, contaminants may adversely affect the effectiveness of a wastewater treatment plant (WWTP). In certain cases, discharged metabolites are transformed back into their pristine structure and become bioactive again.
View Article and Find Full Text PDFThe application of anticancer drugs during pregnancy is associated with placenta-related adverse pregnancy outcomes. Therefore, it is important to study placental toxicity of anticancer drugs. The aim of this study was to compare effects on viability and steroidogenesis in placental tissue explants and trophoblast cell lines.
View Article and Find Full Text PDFBackground: Enalapril is often used in the treatment of cardiovascular diseases. Clinical data suggest that the urinary excretion of enalaprilat, the active metabolite of enalapril, is mediated by renal transporters. We aimed to identify enalaprilat specificity for renal proximal tubular transporters.
View Article and Find Full Text PDFTumor necrosis factor (TNF) inhibitors are increasingly applied during pregnancy without clear knowledge of the impact on placenta and fetus. We assessed placental transfer and exposure to infliximab (n = 3) and etanercept (n = 3) in women with autoimmune diseases. Furthermore, we perfused healthy term placentas for 6 hours with 100 µg/mL infliximab (n = 4) or etanercept (n = 5).
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