TY  - JOUR
AU  - Barri, Thaer
AU  - Trtić-Petrović, Tatjana M.
AU  - Karlsson, Michael
AU  - Jonsson, Jan Ake
PY  - 2008
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3525
AB  - The technique equilibrium sampling through membrane (ESTM) was extended to measuring the free drug concentration in solutions of drug and protein. Bjerrum and Scatchard plots were employed for characterizing individual drug binding to pure human blood proteins. Four drugs were investigated as a model system: fluvoxamine and ropivacaine which dominantly bind to alpha-acid glycoprotein (AGP), and R,S-ibuprofen and S-ketoprofen which highly bind to human serum albumin (HSA). The level of drug binding to AGP and HSA relied on drug and protein concentrations. Bjerrum and Scatchard plots revealed high affinity constants (K-a) at low protein concentration. Both Bjerrum and Scatchard plots of fluvoxamine and ne binding to AGP showed one specific binding site (n(1) = 1) with ropivacaine K-a value close to 5 ropivacaine K-a value close to 5 times higher than the K-a of fluvoxamine at 22.9 mu M AGP concentration. Bjerrum plots of ketoprofen and ibuprofen gave total number of binding sites or bound molecules of 6-7, which did not depend on the drug or protein concentration. Scatchard plots of ketoprofen and ibuprofen exhibited two binding sites (n(1) and n(2)) at 0.15 mu M and 0.75 mu M HSA concentrations. On one hand, at 0.15 mu M HSA, ketoprofen and ibuprofen were bound to site I at n(1) = 1.2 and n(1) = 1.0, respectively. However, at 0.75 mu M HSA, ketoprofen and ibuprofen were bound to site I at n(1) = 1.2 and n(1) = 1.9, respectively. On the other hand, site 11, at 0.15 mu M HSA, interacted with ketoprofen and ibuprofen at n(2) = 5.6 and 6.7, respectively. However, at 0.75 mu M HSA, site II interacted with ketoprofen at n(2) = 7.4 and ibuprofen at n(2) = 6.2. It would be concluded that, upon mixing ketoprofen and ibuprofen in a HSA solution, a ketoprofen-ibuprofen interaction would most likely occur at site II in HSA. (c) 2008 Elsevier B.V. All rights reserved.
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Characterization of drug-protein binding process by employing equilibrium sampling through hollow-fiber supported liquid membrane and Bjerrum and Scatchard plots
VL  - 48
IS  - 1
SP  - 49
EP  - 56
DO  - 10.1016/j.jpba.2008.04.030
ER  - 

@article{
author = "Barri, Thaer and Trtić-Petrović, Tatjana M. and Karlsson, Michael and Jonsson, Jan Ake",
year = "2008",
abstract = "The technique equilibrium sampling through membrane (ESTM) was extended to measuring the free drug concentration in solutions of drug and protein. Bjerrum and Scatchard plots were employed for characterizing individual drug binding to pure human blood proteins. Four drugs were investigated as a model system: fluvoxamine and ropivacaine which dominantly bind to alpha-acid glycoprotein (AGP), and R,S-ibuprofen and S-ketoprofen which highly bind to human serum albumin (HSA). The level of drug binding to AGP and HSA relied on drug and protein concentrations. Bjerrum and Scatchard plots revealed high affinity constants (K-a) at low protein concentration. Both Bjerrum and Scatchard plots of fluvoxamine and ne binding to AGP showed one specific binding site (n(1) = 1) with ropivacaine K-a value close to 5 ropivacaine K-a value close to 5 times higher than the K-a of fluvoxamine at 22.9 mu M AGP concentration. Bjerrum plots of ketoprofen and ibuprofen gave total number of binding sites or bound molecules of 6-7, which did not depend on the drug or protein concentration. Scatchard plots of ketoprofen and ibuprofen exhibited two binding sites (n(1) and n(2)) at 0.15 mu M and 0.75 mu M HSA concentrations. On one hand, at 0.15 mu M HSA, ketoprofen and ibuprofen were bound to site I at n(1) = 1.2 and n(1) = 1.0, respectively. However, at 0.75 mu M HSA, ketoprofen and ibuprofen were bound to site I at n(1) = 1.2 and n(1) = 1.9, respectively. On the other hand, site 11, at 0.15 mu M HSA, interacted with ketoprofen and ibuprofen at n(2) = 5.6 and 6.7, respectively. However, at 0.75 mu M HSA, site II interacted with ketoprofen at n(2) = 7.4 and ibuprofen at n(2) = 6.2. It would be concluded that, upon mixing ketoprofen and ibuprofen in a HSA solution, a ketoprofen-ibuprofen interaction would most likely occur at site II in HSA. (c) 2008 Elsevier B.V. All rights reserved.",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Characterization of drug-protein binding process by employing equilibrium sampling through hollow-fiber supported liquid membrane and Bjerrum and Scatchard plots",
volume = "48",
number = "1",
pages = "49-56",
doi = "10.1016/j.jpba.2008.04.030"
}

Barri, T., Trtić-Petrović, T. M., Karlsson, M.,& Jonsson, J. A.. (2008). Characterization of drug-protein binding process by employing equilibrium sampling through hollow-fiber supported liquid membrane and Bjerrum and Scatchard plots. in Journal of Pharmaceutical and Biomedical Analysis, 48(1), 49-56.
https://doi.org/10.1016/j.jpba.2008.04.030

Barri T, Trtić-Petrović TM, Karlsson M, Jonsson JA. Characterization of drug-protein binding process by employing equilibrium sampling through hollow-fiber supported liquid membrane and Bjerrum and Scatchard plots. in Journal of Pharmaceutical and Biomedical Analysis. 2008;48(1):49-56.
doi:10.1016/j.jpba.2008.04.030 .

Barri, Thaer, Trtić-Petrović, Tatjana M., Karlsson, Michael, Jonsson, Jan Ake, "Characterization of drug-protein binding process by employing equilibrium sampling through hollow-fiber supported liquid membrane and Bjerrum and Scatchard plots" in Journal of Pharmaceutical and Biomedical Analysis, 48, no. 1 (2008):49-56,
https://doi.org/10.1016/j.jpba.2008.04.030 . .