scholarly journals Antiretroviral drug concentrations in brain tissue of adult decedents

AIDS ◽  
2020 ◽  
Vol 34 (13) ◽  
pp. 1907-1914 ◽  
Author(s):  
Micol Ferrara ◽  
Namandjé N. Bumpus ◽  
Qing Ma ◽  
Ronald J. Ellis ◽  
Virawudh Soontornniyomkij ◽  
...  
2019 ◽  
Vol 80 (4) ◽  
pp. 467-473
Author(s):  
Nicole L. Davis ◽  
Amanda Corbett ◽  
Josh Kaullen ◽  
Julie A. E. Nelson ◽  
Charles S. Chasela ◽  
...  

2001 ◽  
Vol 45 (10) ◽  
pp. 2902-2907 ◽  
Author(s):  
Rieneke M. E. van Praag ◽  
Sjoerd Repping ◽  
Jan W. A. de Vries ◽  
Joep M. A. Lange ◽  
Richard M. W. Hoetelmans ◽  
...  

ABSTRACT Limited data are available on antiretroviral drug concentrations in seminal plasma during a dosing interval. Further, since human ejaculate is composed of fluids originating from the testes, the seminal vesicles, and the prostate, all having different physiological characteristics, drug concentrations in total seminal plasma do not necessarily reflect concentrations in the separate compartments. Five human immunodeficiency virus type 1-infected patients on nevirapine (NVP; 200 mg twice a day [b.i.d.]) and/or indinavir (IDV; 800 mg b.i.d. with ritonavir, 100 mg b.i.d.) regimens used a split ejaculate technique to separate seminal plasma in two fractions, representing fluids from the testes and prostate (first fraction) and fluids from the seminal vesicles (second fraction). Split-ejaculate samples were provided at 0, 2, 5, and 8 h after drug ingestion, on separate days after 3 days of sexual abstinence. NVP and IDV showed time-dependent concentrations in seminal plasma, with peak concentrations in both fractions at 2 and 2 to 5 h, respectively, after drug ingestion. The NVP concentrations were not significantly different between the first and second fractions of the ejaculate at all time points measured and were in the therapeutic range, except for the predose concentration in two patients. The median (range) predose IDV concentrations in the first and second fractions of the ejaculate were 448 (353 to 1,015) ng/ml and 527 (240 to 849) ng/ml, respectively (P = 0.7). In conclusion, NVP and IDV concentrations in seminal plasma are dependent on the time after drug ingestion. Furthermore, our data suggest that NVP and IDV achieve therapeutic concentrations in both the testes and prostate and the seminal vesicles throughout the dosing interval.


2014 ◽  
Vol 210 (5) ◽  
pp. 736-744 ◽  
Author(s):  
Anandi N. Sheth ◽  
Tammy Evans-Strickfaden ◽  
Richard Haaland ◽  
Amy Martin ◽  
Chelsea Gatcliffe ◽  
...  

2011 ◽  
Vol 84 (6) ◽  
pp. 878-882 ◽  
Author(s):  
Rebecca Dillingham ◽  
Daniel Fitzgerald ◽  
Etna Eyma ◽  
Erica Miller ◽  
Angela Kashuba ◽  
...  

2001 ◽  
Vol 21 (11) ◽  
pp. 1259-1267 ◽  
Author(s):  
Niklas Marklund ◽  
Tommy Lewander ◽  
Fredrik Clausen ◽  
Lars Hillered

In previous studies, the authors showed that the nitrone radical scavenger α-phenyl-N- tert-butyl nitrone (PBN) and its sulfo-derivative, 2-sulfo-phenyl-N- tert-butyl nitrone (S-PBN), attenuated cognitive disturbance and reduced tissue damage after traumatic brain injury (TBI) in rats. In the current study, the production of reactive oxygen species (ROS) after TBI was monitored with microdialysis and the 4-hydroxybenzoic acid (4-HBA) trapping method. A single dose of PBN (30 mg/kg) or an equimolar dose of S-PBN (47 mg/kg) was administered intravenously 30 minutes before a controlled cortical contusion injury in rats. Plasma and brain tissue drug concentrations were analyzed at the end of the microdialysis experiment (3 hours after injury) and, in a separate experiment with S-PBN, at 30 and 60 minutes after injury. Traumatic brain injury caused a significant increase in ROS formation that lasted for 60 minutes after the injury as evidenced by increased 3,4-dihydroxybenzoic acid (3,4-DHBA) concentrations in the dialysate. PBN and S-PBN equally and significantly attenuated the posttraumatic increase in 3,4-DHBA formation. High PBN concentrations were found bilaterally in brain tissue up to 3 hours after injury. In contrast, S-PBN was rapidly cleared from the circulation and was not detectable in brain at 30 minutes after injury or at any later time point. The results suggest that scavenging of ROS after TBI may contribute to the neuroprotective properties observed with nitrone spin-trapping agents. S-PBN, which remained undetectable even in traumatized brain tissue, reduced ROS production to the same extent as PBN that readily crossed the blood–brain barrier. This finding supports an important role for ROS production at the blood–endothelial interface in TBI.


2021 ◽  
Vol 15 ◽  
Author(s):  
Zachary Geiger ◽  
Brett VanVeller ◽  
Zarin Lopez ◽  
Abdel K. Harrata ◽  
Kathryn Battani ◽  
...  

Ketamine has been in use for over 50 years as a general anesthetic, acting primarily through blockade of N-methyl-D-aspartate receptors in the brain. Recent studies have demonstrated that ketamine also acts as a potent and rapid-acting antidepressant when administered at sub-anesthetic doses. However, the precise mechanism behind this effect remains unclear. We examined the diffusion properties of ketamine in brain tissue to determine their effects in in vitro studies related to the antidepressant action of ketamine. Brain slices from adult mice were exposed to artificial cerebrospinal fluid (aCSF) containing ∼17 μM ketamine HCl for varying amounts of time. The amount of ketamine within each slice was then measured by tandem high-performance liquid chromatography – mass spectrometry to characterize the diffusion of ketamine into brain tissue over time. We successfully modeled the diffusion of ketamine into brain tissue using a mono-exponential function with a time constant of τ = 6.59 min. This curve was then compared to a one-dimensional model of diffusion yielding a diffusion coefficient of approximately 0.12 cm2⋅s–1 for ketamine diffusing into brain tissue. The brain:aCSF partition coefficient for ketamine was determined to be approximately 2.76. Our results suggest that the diffusion properties of ketamine have a significant effect on drug concentrations achieved within brain tissue during in vitro experiments. This information is vital to determine the ketamine concentration necessary for in vitro slice preparation to accurately reflect in vivo doses responsible for its antidepressant actions.


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