NDLI: Effects on Pharmacokinetics of Propranolol and Other Factors in Rats After Acute Exposure to High Altitude at 4,010 m

Content Provider	Springer Nature Link
Author	Wenbin, Li Rong, Wang Hua, Xie Juanhong, Zhang Xiaoyu, Wu Zhengping, Jia
Copyright Year	2014
Abstract	A series of pathological, physiological, and biochemical changes, even anatomical histological changes happen while humans arrive at the high plateau region from plain area. There is a certain relationship between the body’s compensatory or decompensated adjustments to the environment and the changes of absorption, distribution, metabolism, and excretion of drugs. The objective of the study is to observe the effects of acute exposure to high altitude at 4,010 m on pharmacokinetics of propranolol in rats, and to provide basis and new ideas to adjust drug dosage and administration, so as to promote rational drug use in high altitude. 28 healthy male wistar rats were randomly divided into four groups, group A and B which were in plain area; group C and D which were acutely exposed to high altitude by aviation; group A and C were used for pharmacokinetics determination of propranolol, while group B and D had no drug administration for physiological and pathological changes research at high altitude. The pharmacokinetics of propranolol significantly changed; area under curve, C $_{max}$ (the peak concentration), mean residence time, and t $_{1/2}$ (the biological half-life) increased significantly by 481.72, 398.94, 44.87, and 58.77 %, respectively; clearance and V (apparent volume of distribution) decreased by 81.50 and 70.56 %, respectively, after acute exposure to high altitude at 4,010 m; Analytic results show that pH, buffer base, base excess, ctCO$_{2}$ (content of total carbon dioxide), sO$_{2}$ (oxygen saturation of arterial blood), pO$_{2}$ (oxygen tension of arterial blood), and cNa$^{+}$ severely decreased by 2.43, 630.00, 311.00, 11.48, 91.38, 76.22, and 2.82 %, respectively, while pCO$_{2}$ (carbon dioxide tension of arterial blood) and cCl$^{−}$ significantly increased by 47.40 and 6.76 %. Lactate dehydrogenase and total protein significantly decreased by 58.44 and 26.82 %, while total bilirubin and alkaline phosphatase severely increased by 338 and 24.94 % after acute exposure to high altitude at 4,010 m. Pathological research shows that alveolar wall is hyperemic, edematous, and incrassate; alveolus epithelium becomes hyperplastic while neutrophilic granulocytes infiltrate; brain neurons are edematous and perivascular space occurred; neurons of seahorse are metamorphic and karyopyknotic; mesangial cells are hyperplastic in kidney glomerulus tissue. We should reduce the dosage or extend the dosing interval in high altitude to maintain the drug concentration in therapeutic window since velocity of metabolism and excretion are reduced.
Starting Page	27
Ending Page	36
Page Count	10
File Format	PDF
ISSN	10859195
Journal	Cell Biochemistry and Biophysics
Volume Number	72
Issue Number	1
e-ISSN	15590283
Language	English
Publisher	Springer US
Publisher Date	2014-11-23
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	High altitude Propranolol Pharmacokinetics Blood gas analysis Biochemical indicator analysis CYP1A2 Biochemistry Pharmacology/Toxicology Biotechnology Cell Biology Biophysics and Biological Physics
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Biochemistry Biophysics

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