Abstract
The interaction between 18-methyl norethindrone and ketoprofen, including the displacement of ketoprofen from human serum albumin binding sites, was investigated by the capillary electrophoresis-frontal analysis method (CE-FA) at room temperature. A very large sample plug was introduced hydrostatically into the capillary (65 cm × 50 μm i.d.; effective length of 35 cm) over 80 s at a height difference of 11 cm. The working conditions for CE-FA separation are as follows: operating voltage, 10 kV; running buffer, 67 mmol·L−1 phosphate, pH 7.4. The unbound ketoprofen concentration was directly measured from the height of the frontal peak. When the concentration of 18-methyl norethindrone was increased from 0 to 200 μmol/L, the unbound ketoprofen concentration was found to increase from 22.4 to 26.4 μmol/L at 100 μmol/L total ketoprofen concentration and from 82.1 to 106.2 μmol/L at 200 μmol/L total ketoprofen concentration. From these data, it may be deduced that the administration of high concentration of 18-methyl norethindrone can displace ketoprofen from its secondary binding site.
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References
Stockley I.-H., Drug interactions. A source book of adverse interactions, their mechanisms, clinical importance and management, Blackwell scientific publications, oxford London Edinburgh. 1981: 4–5.
Pouplana R., Lozano J.-J. and Ruiz J.-J., Molecular modelling of the differential interaction between several non-steroidal anti-inflammatory drugs and human prostaglandin endoperoxide H synthase-2 (h-PGHS-2), J. Mol. Graph. Model, 2002 20: 329–343.
Miranda H.-F., Sierralta F. and Pinardi G., Neostigmine interactions with non steroidal anti-inflammatory drugs, Br. J. Pharmacol, 2002 135: 1591–1597.
Walle U.-K., Fagan T.-C., Topmiller M.-J., Conradi E.-C. and Walle T., The influence of gender and sex steroid hormones on the plasma binding of propranolol enantiomers, Br. J. Clin. Pharmacol., 1994 37: 21–25.
Yu H.-Y. and Shen Y.-Z., Displacement effect of valproate on bilirubin-albumin binding in human plasma, J. Formos. Med. Assoc., 1999 98: 201–204.
Wang H, Zou H. and Zhang Y., Quantitative study of competitive binding of drugs to protein by microdialysis/high-performance liquid chromatography, Anal. Chem., 1998 70: 373–377.
Yamasaki K., Rahman M.-H., Tsutsumi Y., Maruyama T., Ahmed S., Kragh-Hansen U. and Otagiri M., Circular dichroism simulation shows a site-II-to-site-I displacement of human serum albumin-bound diclofenac by ibuprofen, AAPS PharmSciTech, 2000 1: E12.
Shimura K. and Kasai K.-I., Review Affinity capillary electrophoresis: a sensitive tool for the study of molecular interactions and its use in microscale analyses, Anal. Biochem., 1997 251: 1–16.
Busch M.-H.-A., Carels L.-B., Boelens H.-F.-M., Kraak J.-C. and Poppe H, Comparison of five methods for the study of drug-protein binding in affinity capillary electrophoresis, J. Chromatogr. A, 1997 777: 311–328.
Sihvo S., Klaukka T., Martikainen J. and Hemminki E., Frequency of daily over-the-counter drug use and potential clinically significant over-the-counter-prescription drug interactions in the Finnish adult population, Eur. J. Clin. Pharmacol., 2000 56: 495–499.
Miranda H.-F., Sierralta F. and Pinardi G., Neostigmine interactions with non steroidal anti-inflammatory drugs, Br. J. Pharmacol, 2002 135: 1591–1597.
Li Q.-G. and Humpel M, Serum protein binding characteristics of cyproterone acetate, gestodene, levonorgestrel and norethisterone in rat, rabbit, dog, monkey and man, J. Steroid Biochem., 1990 35: 319–326.
Doose D.-R., Wang S.-S., Padmanabhan M., Schwabe S., Jacobs D. and Bialer M., Effect of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects, Epilepsia, 2003 44: 540–549.
Fung Y.-S., Sun D.-X. and Yeung C.-Y., Capillary electrophoresis for determination of unbound and albumin-bound bilirub in and the investigation of drug interaction with bilirubin-bound albumin, Electrophoresis, 2000 21: 403–410.
Østergaard J., Schou C., Larsen C. and Heegaard N.-H.-H., Evaluation of capillary electrophoresis-frontal analysis for the study of low molecular weight drug-human serum albumin interactions, Electrophoresis, 2002 23: 2842–2853.
Li F., Zhou D. and Guo X., Study on protein binding of ketoprofen using capillary electrophoresis frontal analysis compared with liquid chromatography frontal analysis, J. Chromatogr. Sci., 2003 41: 137–141.
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Translated from Chinese Journal of Chromatography, 2005, 23(2)(in Chinese)
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Zhou, D., Famei, L. Tudy on drug displacement interactions by capillary electrophoresis-frontal analysis. Front. Chem. China 1, 207–210 (2006). https://doi.org/10.1007/s11458-006-0009-x
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DOI: https://doi.org/10.1007/s11458-006-0009-x