Plasma carboxylesterase 1 predicts methylphenidate exposure: a proof‐of‐concept study using plasma protein biomarker for hepatic drug metabolism

Author(s):  
Jian Shi ◽  
Jingcheng Xiao ◽  
Xinwen Wang ◽  
Sun Min Jung ◽  
Barry E. Bleske ◽  
...  
2020 ◽  
Vol 88 (4) ◽  
pp. 45
Author(s):  
Silviya Abarova ◽  
Lyubka Tancheva ◽  
Rumen Nikolov ◽  
Julia Serkedjieva ◽  
Elitsa Pavlova ◽  
...  

The decreased hepatic drug metabolism (predominately first phase) is one of the essential reasons for numerous side effects and for increased drug toxicity during influenza virus infection (IVI). The present study aims to investigate some mechanisms of the preventive effect of a standardized polyphenol complex from the medicinal plant Geranium sanguineum L. (PPhC) (10 mg/kg nasally). A verified experimental model of IVI A/Aichi/2/68 (H3N2) (4.5 lg LD50) in male ICR (Institute of Cancer Research, USA) mice was used. Changes in hepatic monooxygenase activities as well as nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome C reductase activity and cytochtome P450 content were studied on days 2, 6, 9, 21 of the infection together with thiobarbituric acid reactive substances in the liver supernatant. Our data clearly demonstrates that IVI affects all components of the electronic chain of cytochrome P-450. N-demethylases and hydroxylases as well as the activity of cytochrome C reductase and cytochtome P-450 content were decreased in the course of the virus infection. This implies that free radicals play an important role not only in the pathogenesis of IVI, but also in the modulation of the hepatic monooxygenase activity. This is also consistent with the established polyphenol complex PPhC from the medicinal plant Geranium sanguineum L. preventive effect against increased thiobarbituric acid reactive substances (TBARS)-levels. PPhC restored most of the monooxygenase activities that were inhibited in IVI animals, even over the control levels, probably via multiple mechanisms that may entail antioxidant activity and selective antiviral and protein-binding effects. In contrast to infected animals, in healthy mice, PPhC showed moderate reversible inhibitory effect on hepatic monooxygenase activities.


2001 ◽  
Vol 71 (11) ◽  
pp. 1585-1592 ◽  
Author(s):  
Shuang Bai ◽  
Lane J. Brunner ◽  
Stanislaw M. Stepkowski ◽  
Kimberly L. Napoli ◽  
Barry D. Kahan

JAMA ◽  
1976 ◽  
Vol 236 (14) ◽  
pp. 1612
Author(s):  
Nicholas F. LaRusso

1963 ◽  
Vol 12 (4) ◽  
pp. 341-348 ◽  
Author(s):  
Larry A. Rogers ◽  
Robert L. Dixon ◽  
James R. Fouts

1973 ◽  
Vol 51 (1) ◽  
pp. 6-11 ◽  
Author(s):  
G. C. Becking

The effect of vitamin A status on hepatic drug metabolism was studied in rats. Animals were fed diets with and without vitamin A for 20 and 25 days. Weight gains of control and deficient animals were not significantly different, whereas liver vitamin A levels had decreased to less than 10% of control animals after 20 days and were essentially zero after eating the deficient diet for 25 days. Aniline metabolism in vitro and aminopyrine metabolism in vitro and in vivo were significantly lower in male weanling rats fed a vitamin A deficient diet for 20 days. No alteration in in vitro p-nitrobenzoic acid metabolism was noted after 25 days on the test. Vitamin A deficiency did not alter microsomal protein levels or cytochrome c reductase activity but deficient animals did have a lower microsomal cytochrome P-450 content. Hepatic enzyme activities and cytochrome P-450 levels were restored to values approaching those found in control animals by feeding vitamin A deficient rats the vitamin A containing diet for 21 days. Liver vitamin A levels were markedly increased after re-feeding studies but were still significantly lower than control animals.


2005 ◽  
Vol 1 (1) ◽  
pp. 75-90 ◽  
Author(s):  
Marc Vermeir ◽  
Pieter Annaert ◽  
Rao NVS Mamidi ◽  
Dirk Roymans ◽  
Willem Meuldermans ◽  
...  

Author(s):  
E. Altomare ◽  
G. Vendemiale ◽  
T. Trizio ◽  
G. Pallasciano ◽  
O. Albano

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