Comparison of tenofovir plasma and tissue exposure using a population pharmacokinetic model and bootstrap: a simulation study from observed data

AbstractSparse tissue sampling with intensive plasma sampling creates a unique data analysis problem in determining drug exposure in clinically relevant tissues. Tissue exposure may govern drug efficacy, as many drugs exert their actions in tissues. We compared tissue area-under-the-curve (AUC) generated from bootstrapped noncompartmental analysis (NCA) methods and compartmental nonlinear mixed effect (NLME) modeling. A model of observed data after single-dose tenofovir disoproxil fumarate was used to simulate plasma and tissue concentrations for two destructive tissue sampling schemes. Two groups of 100 data sets with densely-sampled plasma and one tissue sample per individual were created. The bootstrapped NCA (SAS 9.3) used a trapezoidal method to calculate geometric mean tissue AUC per dataset. For NLME, individual post hoc estimates of tissue AUC were determined, and the geometric mean from each dataset calculated. Median normalized prediction error (NPE) and absolute normalized prediction error (ANPE) were calculated for each method from the true values of the modeled concentrations. Both methods produced similar tissue AUC estimates close to true values. Although the NLME-generated AUC estimates had larger NPEs, it had smaller ANPEs. Overall, NLME NPEs showed AUC under-prediction but improved precision and fewer outliers. The bootstrapped NCA method produced more accurate estimates but with some NPEs  >  100%. In general, NLME is preferred, as it accommoda...
Source: Journal of Pharmacokinetics and Pharmacodynamics - Category: Drugs & Pharmacology Source Type: research

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Publication date: Available online 21 January 2020Source: The Lancet PsychiatryAuthor(s): Chido Rwafa-Madzvamutse, Khameer Kidia, Oye Gureje, Walter Mangezi, Helen E Jack
Source: The Lancet Psychiatry - Category: Psychiatry Source Type: research
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Source: The Lancet Psychiatry - Category: Psychiatry Source Type: research
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Source: The Lancet Psychiatry - Category: Psychiatry Source Type: research
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Source: The Lancet Psychiatry - Category: Psychiatry Source Type: research
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Source: Journal of Obsessive Compulsive and Related Disorders - Category: Psychiatry Source Type: research
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Source: Acta Pharmaceutica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharm Source Type: research
Abstract The introduction of the second generation triptans in clinical and experimental practice was a major progress in the pharmacotherapy of migraine. Frovatriptan is a second generation triptan with strong 5-HT1B/1D serotonergic agonism and low 5-HT1A/7 receptor affinity, while almotriptan possesses not only the typical 5-HT1B/1D receptor agonist activity, but shows an affinity to the 5-HT1F receptor. The aim of our study was to assess the impact of frovatriptan and almotriptan on hemodynamics in male and female rats. We used a non-invasive "tail-cuff" method to measure the arterial blood pressure. ...
Source: Acta Pharmaceutica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharm Source Type: research
This study evaluated the antioxidant and antidiabetic properties of a heliangolide sesquiterpene lactone isolated from Helianthus annuus L. leaves. The heliangolide sesquiterpene lactone was isolated through a combination of solvent-solvent partitioning, column chromatography, thin layer chromatography and high-performance liquid chromatography techniques. The antioxidant activity of the compound was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide radical scavenging assays while the antidiabetic effects were investigated in alloxan-induced diabetic rats. The heliangolide derivative at the concentratio...
Source: Acta Pharmaceutica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharm Source Type: research
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Source: Acta Pharmaceutica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharm Source Type: research
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Source: Acta Pharmaceutica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharm Source Type: research
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