Ritonavir- or cobicistat-boosted antiretroviral therapy and direct oral anticoagulants: A case for apixaban.

The potential for drug-drug interactions (DDIs) between direct oral anticoagulants and antiretroviral therapy (ART) is vast. Ritonavir and cobicistat are used as pharmacokinetic enhancers with either concurrent protease inhibitors or the integrase strand transfer inhibitor, elvitegravir, to optimize therapeutic concentrations by cytochrome P450 (CYP) inhibition. To date, only rivaroxaban and dabigatran have reported cases of use with ritonavir-boosted ART. Apixaban is metabolized similarly to rivaroxaban, but offers a dose reduction in the case of major DDIs. We report the successful use of reduced-dose apixaban to treat and prevent thromboembolic complications in six persons living with human immunodeficiency virus (HIV) on ritonavir- or cobicistat-boosted ART. This case series and available literature support the use of apixaban or dabigatran, depending on the boosted ART regimen.

Arsenic Speciation of Contaminated Soils / Solid Wastes and Relative Oral Bioavailability in Swine and Mice.

Arsenic (As) is one of the most widespread, toxic elements in the environment and human activities have resulted in a large number of contaminated areas. However abundant, the potential of As toxicity from exposure to contaminated soils is limited to the fraction that will dissolve in the gastrointestinal system and be absorbed into systemic circulation or bioavailable species. In part, the release of As from contaminated soil to gastrointestinal fluid depends on the form of solid phase As also termed "As speciation." In this study, 27 As-contaminated soils and solid wastes were analyzed using X-ray absorption spectroscopy (XAS) and results were compared to in vivo bioavailability values determined using the adult mouse and juvenile swine bioassays. Arsenic bioavailability was lowest for soils that contained large amounts of arsenopyrite and highest for materials that contained large amounts of ferric arsenates. Soil and solid waste type and properties rather than the contamination source had the greatest influence on As speciation. Principal component analysis determined that As(V) adsorbed and ferric arsenates were the dominant species that control As speciation in the selected materials. Multiple linear regression (MLR) was used to determine the ability of As speciation to predict bioavailability. Arsenic speciation was predictive of 27% and 16% of RBA As determined using the juvenile swine and adult mouse models, respectively. Arsenic speciation can provide a conservative estimate of RBA As using MLR for the juvenile swine and adult mouse bioassays at 55% and 53%, respectively.

Phosphorus Amendment Efficacy for In Situ Remediation of Soil Lead Depends on the Bioaccessible Method.

A validated method is needed to measure reductions of in vitro bioaccessible (IVBA) Pb in urban soil remediated with amendments. This study evaluated the effect of in vitro extraction solution pH and glycine buffer on bioaccessible Pb in P-treated soils. Two Pb-contaminated soils (790-1300 mg Pb kg), one from a garden and one from a city lot in Cleveland, OH, were incubated in a bench scale experiment for 1 yr. Six phosphate amendments, including bone meal, fish bone, poultry litter, monoammonium phosphate, diammonium phosphate, and triple superphosphate, were added to containers at two application rates. Lead IVBA was assessed using USEPA Method 1340 and three modified versions of this method. Modifications included using solutions with pH 1.5 and 2.5 as well as using solutions with and without 0.4 mol L glycine. Soil amendments were ineffective in reducing IVBA Pb in these soils as measured by pH 1.5 with glycine buffer. The greatest reductions in IVBA Pb, from 5 to 26%, were found using pH 2.5 extractions. Lead mineral results showed several soil amendments promoted Pb phosphate formation, an indicator of remediation success. A significant negative linear relationship between reduction in IVBA Pb and Pb-phosphate formation was found only for pH 2.5 without glycine extraction solution. A modified USEPA Method 1340 without glycine and using pH 2.5 has the potential to predict P soil treatment efficacy and reductions in bioavailable Pb.