Objective: To evaluate elvitegravir and cobicistat pharmacokinetics during pregnancy compared to postpartum and in infant washout samples after delivery. Design: Nonrandomized, open-label, parallel-group, multi-center phase-IV prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women and their children in the U.S. Methods: Intensive steady-state 24 hour pharmacokinetic profiles after 150 mg of elvitegravir and 150 mg of cobicistat given orally in fixed dose combination once-daily were performed during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Elvitegravir and cobicistat were measured in plasma by a validated LC-MS/MS assay with a lower quantitation limit of 10 ng/mL. A two-tailed Wilcoxon signed-rank test (α = 0.10) was employed for paired within-participant comparisons. Results: Thirty pregnant women taking elvitegravir and cobicistat once-daily enrolled in the study. Compared to paired postpartum data, elvitegravir AUC0–24 was 24% lower in the second trimester (n=14, P=0.058, GMR=0.76, 90% CI 0.57–1.0) and 44% lower in the third trimester (n=24, P=0.0001, GMR=0.56, 90% CI 0.42–0.73), while cobicistat AUC0–24 was 44% lower in the second trimester (n=14, P=0.0085, GMR=0.56, 90% CI 0.37 – 0.85) and 59% lower in the third trimester (n=24, p<.0001, GMR=0.41, 90% CI 0.30 – 0.57). Median cord blood elvitegravir concentration was 540.6 ng/mL and the median ratio of cord blood to maternal plasma elvitegravir concentrations was 0.91. Conclusions: Standard elvitegravir and cobicistat dosing during pregnancy results in significantly lower exposure which may increase the risk of virologic failure and mother-to-child transmission. Additional studies are needed to optimize elvitegravir and cobicistat dosing regimens in pregnant women.
In this study, aquatic plants in a small reservoir were detected using multispectral UAV (Unmanned Aerial Vehicle) imagery and various vegetation indices. A Firefly UAV, which has both fixed-wing and rotary-wing flight modes, was flown over the study site four times. A RedEdge camera was mounted on the UAV to acquire multispectral images. These images were used to analyze the NDVI (Normalized Difference Vegetation Index), ENDVI (Enhance Normalized Difference Vegetation Index), NDREI (Normalized Difference RedEdge Index), NGRDI (Normalized Green-Red Difference Index), and GNDVI (Green Normalized Difference Vegetation Index). As for multispectral characteristics, waterside plants showed the highest reflectance in Rnir, while floating plants had a higher reflectance in Rre. During the hottest season (on 25 June), the vegetation indices were the highest, and the habitat expanded near the edge of the reservoir. Among the vegetation indices, NDVI was the highest and NGRDI was the lowest. In particular, NGRDI had a higher value on the water surface and was not useful for detecting aquatic plants. NDVI and GNDVI, which showed the clearest difference between aquatic plants and water surface, were determined to be the most effective vegetation indices for detecting aquatic plants. Accordingly, the vegetation indices using multispectral UAV imagery turned out to be effective for detecting aquatic plants. A further study will be accompanied by a field survey in order to acquire and analyze more accurate imagery information.
The regulatory framework for considering the fetal effects of new drugs is limited. This is partially due to the fact that pediatric regulations (21 CFR subpart D) do not apply to the fetus, and only US Health and Human Service (HHS) regulations apply to the fetus. The HHS regulation 45 CFR Part 46 Subpart B limits research approvable by an institutional review board to research where the risk to the fetus is minimal unless the research holds out the prospect of a direct benefit to the fetus or the pregnant woman (45 CFR 46.204). Research that does not meet these requirements, but presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health of pregnant women, fetuses, or neonates, may be permitted by the Secretary of the HHS after expert panel consultation and opportunity for public review and comment (45 CFR 46.407). If the product is regulated by the US Food and Drug Administration (FDA), FDA may get involved in the review process. The FDA does however have a Reviewer Guidance on Evaluating the Risks of Drug Exposure in Human Pregnancies from 2005 and this guidance does discuss the intensity of drug exposure. Estimation of that exposure using physiologically based pharmacokinetic (PBPK) modeling has been suggested by some investigators. Given that drug exposure during pregnancy will impact the fetus, a number of new guidances in the last 2 years also address inclusion of pregnant women in clinical drug trials. Therefore, the drug-specific information on fetal pharmacology will increase dramatically in the next decade due to interest in drugs administered in pregnancy and with the assistance of model-informed drug development.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.