Fundamentals of Pharmacokinetics to Assess the Correlation Between Plasma Drug Concentrations and Different Blood Sampling Methods

碩士 === 國防醫學院 === 藥學研究所 === 106 === Introduction: During drug discovery, animal studies are inevitable to test the pharmacokinetics of novel drugs. Owing to various factors related to restrictions in experimental implementation and study objectives, selection of appropriate sampling methods is extrem...

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Main Authors: CHEN, WEI-CHING, 陳薇晴
Other Authors: WANG, HONG-JAAN
Format: Others
Language:zh-TW
Published: 2018
Online Access:http://ndltd.ncl.edu.tw/handle/r8q7f5
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spelling ndltd-TW-106NDMC05510032019-11-21T05:33:38Z http://ndltd.ncl.edu.tw/handle/r8q7f5 Fundamentals of Pharmacokinetics to Assess the Correlation Between Plasma Drug Concentrations and Different Blood Sampling Methods 以藥物動力學評估血中藥物濃度與不同血液取樣方法之間的相關性 CHEN, WEI-CHING 陳薇晴 碩士 國防醫學院 藥學研究所 106 Introduction: During drug discovery, animal studies are inevitable to test the pharmacokinetics of novel drugs. Owing to various factors related to restrictions in experimental implementation and study objectives, selection of appropriate sampling methods is extremely important in animal studies. Many blood collection methods have been used in previous studies; however, the influence of different blood sampling methods on plasma drug concentrations has not yet been determined. Several studies have pointed out that drug concentrations may vary depending on the sampling method used, but some studies have shown opposing results, indicating that the blood collection method has no influence on drug concentration. In this study, we aimed to determine whether blood concentration of the target drug changes based on the blood collection site. Methods: We compared three commonly used blood sampling methods for small animals: carotid artery cannulation, temporary cannulation of tail vein, and tail snip bleeding. Based on the pharmacokinetics and physicochemical properties of the compound itself, eight clinical drugs (rifabutin, atorvastatin, simvastatin, nifedipine, pravastatin, atenolol, rosuvastatin and ketorolac) selected from the BDDCS were administered to rats via either intracardiac injection or orally. Blood samples collected from different sampling sites were measured, and the pharmacokinetic properties of all the drugs were evaluated to determine the influence of the sampling site. Results: The results showed that sampling site influenced the pharmacokinetic properties of drugs. Irrespective of oral or intracardiac dosing, the maximum plasma concentration (Cmax) and the area under the curve (AUC0-t) of rifabutin in rats were significantly higher when blood was sampled from the carotid artery than those when collected via the tail vein or tail snip. Additionally, similar results were also observed when nifedipine and atenolol were intracardiac administered to rats. However, the plasma drug concentrations of the other five drugs showed no significant difference in terms of the method used. Conclusion: Compared to the previous reports, we here investigated that certain drugs which are likely to show the discrepancies in the pharmacokinetic determinations due to the sampling sites differences. The volume of drug distribution (VD) which was mentioned in the literature as a factor might not play the sole role. It is believed that many other different factors may potentially cause this difference, even we do not yet clear which one has the most significant impact. However, rate and extent of the drug distribution may have more effects on the plasma drug determinations. In addition, the arterio-venous concentration differences may also play a role in this issue. As we know, the acid-base properties of a drug will affect the rate of drug distribution equilibrium in the central and peripheral compartments, it will further influence the concentration determinations and consequently, alter the pharmacokinetic properties of the determined drug. WANG, HONG-JAAN 王鴻展 2018 學位論文 ; thesis 109 zh-TW
collection NDLTD
language zh-TW
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description 碩士 === 國防醫學院 === 藥學研究所 === 106 === Introduction: During drug discovery, animal studies are inevitable to test the pharmacokinetics of novel drugs. Owing to various factors related to restrictions in experimental implementation and study objectives, selection of appropriate sampling methods is extremely important in animal studies. Many blood collection methods have been used in previous studies; however, the influence of different blood sampling methods on plasma drug concentrations has not yet been determined. Several studies have pointed out that drug concentrations may vary depending on the sampling method used, but some studies have shown opposing results, indicating that the blood collection method has no influence on drug concentration. In this study, we aimed to determine whether blood concentration of the target drug changes based on the blood collection site. Methods: We compared three commonly used blood sampling methods for small animals: carotid artery cannulation, temporary cannulation of tail vein, and tail snip bleeding. Based on the pharmacokinetics and physicochemical properties of the compound itself, eight clinical drugs (rifabutin, atorvastatin, simvastatin, nifedipine, pravastatin, atenolol, rosuvastatin and ketorolac) selected from the BDDCS were administered to rats via either intracardiac injection or orally. Blood samples collected from different sampling sites were measured, and the pharmacokinetic properties of all the drugs were evaluated to determine the influence of the sampling site. Results: The results showed that sampling site influenced the pharmacokinetic properties of drugs. Irrespective of oral or intracardiac dosing, the maximum plasma concentration (Cmax) and the area under the curve (AUC0-t) of rifabutin in rats were significantly higher when blood was sampled from the carotid artery than those when collected via the tail vein or tail snip. Additionally, similar results were also observed when nifedipine and atenolol were intracardiac administered to rats. However, the plasma drug concentrations of the other five drugs showed no significant difference in terms of the method used. Conclusion: Compared to the previous reports, we here investigated that certain drugs which are likely to show the discrepancies in the pharmacokinetic determinations due to the sampling sites differences. The volume of drug distribution (VD) which was mentioned in the literature as a factor might not play the sole role. It is believed that many other different factors may potentially cause this difference, even we do not yet clear which one has the most significant impact. However, rate and extent of the drug distribution may have more effects on the plasma drug determinations. In addition, the arterio-venous concentration differences may also play a role in this issue. As we know, the acid-base properties of a drug will affect the rate of drug distribution equilibrium in the central and peripheral compartments, it will further influence the concentration determinations and consequently, alter the pharmacokinetic properties of the determined drug.
author2 WANG, HONG-JAAN
author_facet WANG, HONG-JAAN
CHEN, WEI-CHING
陳薇晴
author CHEN, WEI-CHING
陳薇晴
spellingShingle CHEN, WEI-CHING
陳薇晴
Fundamentals of Pharmacokinetics to Assess the Correlation Between Plasma Drug Concentrations and Different Blood Sampling Methods
author_sort CHEN, WEI-CHING
title Fundamentals of Pharmacokinetics to Assess the Correlation Between Plasma Drug Concentrations and Different Blood Sampling Methods
title_short Fundamentals of Pharmacokinetics to Assess the Correlation Between Plasma Drug Concentrations and Different Blood Sampling Methods
title_full Fundamentals of Pharmacokinetics to Assess the Correlation Between Plasma Drug Concentrations and Different Blood Sampling Methods
title_fullStr Fundamentals of Pharmacokinetics to Assess the Correlation Between Plasma Drug Concentrations and Different Blood Sampling Methods
title_full_unstemmed Fundamentals of Pharmacokinetics to Assess the Correlation Between Plasma Drug Concentrations and Different Blood Sampling Methods
title_sort fundamentals of pharmacokinetics to assess the correlation between plasma drug concentrations and different blood sampling methods
publishDate 2018
url http://ndltd.ncl.edu.tw/handle/r8q7f5
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