Fundamentals of Pharmacokinetics to Assess the Correlation Between Plasma Drug Concentrations and Different Blood Sampling Methods
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Various blood collection methods were developed and used in the pharmacokinetic evaluation of drugs. However, the influence of different blood sampling methods on plasma drug concentrations has not been clarified. In the present study, we aimed to determine whether the plasma concentration of a target drug changes based on the collection site and elucidate the mechanism responsible for this change.
We compared three blood sampling methods commonly used in small animals. Eight clinical drugs were selected and administered to rats simultaneously via intracardiac injection or oral gavage. Blood samples were collected from different sites at the same individual, and pharmacokinetic properties of the drugs were then evaluated.
Study results showed that the maximum plasma concentration or area under the curve of three study drugs was significantly higher in rats when blood was sampled from the carotid artery than when it was sampled from the caudal vein or by tail snip.
Pharmacokinetics of certain drugs may differ based on the blood sampling site. The acid-base properties of drugs may influence pharmacokinetic evaluation. The rate and extent of drug distribution may also cause such differences and have significant effects on plasma drug levels.
KEY WORDSblood sampling carotid cannulation caudal vein pharmacokinetics tail snip
- 10.de Pont AC, Hofstra JJ, Pik DR, Meijers JC, Schultz MJ. Pharmacokinetics and pharmacodynamics of danaparoid during continuous venovenous hemofiltration: a pilot study. Crit Care. 2007;11(5):R102.Google Scholar
- 14.Ahmad M, Qamar-uz-Zaman M, Madni MA, Minhas M, Atif M, Naveed A, et al. Pharmacokinetic and bioavailability studies of commercially available simvastatin tablets in healthy and moderately hyperlipidemic human subjects. J Chem Soc Pak. 2011;33(1):49–54.Google Scholar
- 15.Gertz M, Harrison A, Houston JB, Galetin A. Prediction of human intestinal first-pass metabolism of 25 CYP3A substrates from in vitro clearance and permeability data. Drug Metab Dispos. 2010;38(7):1147–58.Google Scholar
- 17.Lee JB, Zgair A, Taha DA, Zang X, Kagan L, Kim TH, et al. Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays. Eur J Pharm Biopharm. 2017;114:38–42.Google Scholar
- 18.Li J, Wang Y, Zhang W, Huang Y, Hein K, Hidalgo IJ. The role of a basolateral transporter in rosuvastatin transport and its interplay with apical breast cancer resistance protein in polarized cell monolayer systems. Drug Metab Dispos. 2012;40(11):2102–8.Google Scholar
- 22.U.S. Food and Drug Administration. Bioanalytical method validation guidance for industry. 2018 May 21. Available from: https://www.fda.gov/downloads/drugs/guidances/ucm070107.pdf.
- 23.European medicines agency. Guideline on bioanalytical method validation. 2011 July 21. Available from: https://www.ema.europa.eu/documents/scientific-guideline/guideline-bioanalytical-method-validation_en.pdf.
- 26.Samaja M, Allibardi S, Milano G, Neri G, Grassi B, Gladden LB, et al. Differential depression of myocardial function and metabolism by lactate and H+. Am J Phys. 1999;276(1 Pt 2):H3–8.Google Scholar
- 27.Tsamandouras N, Dickinson G, Guo Y, Hall S, Rostami-Hodjegan A, Galetin A, et al. Development and application of a mechanistic pharmacokinetic model for simvastatin and its active metabolite simvastatin acid using an integrated population PBPK approach. Pharm Res. 2015;32(6):1864–83.CrossRefGoogle Scholar
- 31.Shargel L, Andrew B, Wu-Pong S. Applied biopharmaceutics & pharmacokinetics. New York: McGraw-Hill Medical Publishing Division; 2015.Google Scholar
- 32.Gibaldi M, Perrier D. Pharmacokinetics (Drugs and the Pharmaceutical Sciences). New York: CRC Press; 1982.Google Scholar
- 33.Kwon Y. Handbook of essential pharmacokinetics, pharmacodynamics and drug metabolism for industrial scientists. New York: Springer; 2001.Google Scholar