Abstract
1 Based on the Scatchard plot of the binding data of valproic acid (VPA) it is concluded that the drug is bound by two groups of binding sites with the association constants K1=40.0 X 10(-3) and K2=0.39 X 10(3), and the number of binding sites n1=1.5 and n2=6.8. 2 The binding is dependent on dialysis time, on temperature, on the drug concentration, and on the protein concentration in plasma. 3 At therapeutic plasma concentrations unbound VPA is 8.4 +/- 2.5%, but is increased to 20.3 +/- 4.7% in patients with significant impairment of renal function (P less than 0.001). 4 In patients with renal disease a good correlation is found between unbound VPA and serum creatinine, creatinine clearance, blood nitrogen and uric acid, respectively. A poor correlation is seen between unbound VPA and total protein or albumin concentration in plasma.
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Selected References
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- Affrime M., Reidenberg M. M. The protein binding of some drugs in plasma from patients with alcoholic liver disease. Eur J Clin Pharmacol. 1975 Apr 4;8(3-4):267–269. doi: 10.1007/BF00567126. [DOI] [PubMed] [Google Scholar]
- Feldman H. A. Mathematical theory of complex ligand-binding systems of equilibrium: some methods for parameter fitting. Anal Biochem. 1972 Aug;48(2):317–338. doi: 10.1016/0003-2697(72)90084-x. [DOI] [PubMed] [Google Scholar]
- Gugler R., Azarnoff D. L. Drug protein binding and the nephrotic syndrome. Clin Pharmacokinet. 1976;1(1):25–35. doi: 10.2165/00003088-197601010-00003. [DOI] [PubMed] [Google Scholar]
- Gugler R., Azarnoff D. L., Shoeman D. W. Diphenylhydantoin: correlation between protein binding and albumin concentration. Klin Wochenschr. 1975 May 1;53(9):445–446. doi: 10.1007/BF01493371. [DOI] [PubMed] [Google Scholar]
- Gugler R., Shoeman D. W., Huffman D. H., Cohlmia J. B., Azarnoff D. L. Pharmacokinetics of drugs in patients with the nephrotic syndrome. J Clin Invest. 1975 Jun;55(6):1182–1189. doi: 10.1172/JCI108035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hooper W. D., Bochner F., Eadie M. J., Tyrer J. H. Plasma protein binding of diphenylhydantoin. Effects of sex hormones, renal and hepatic disease. Clin Pharmacol Ther. 1974 Mar;15(3):276–282. doi: 10.1002/cpt1974153276. [DOI] [PubMed] [Google Scholar]
- Koch-Weser J., Sellers E. M. Binding of drugs to serum albumin (first of two parts). N Engl J Med. 1976 Feb 5;294(6):311–316. doi: 10.1056/NEJM197602052940605. [DOI] [PubMed] [Google Scholar]
- Koch-Weser J., Sellers E. M. Drug therapy. Binding of drugs to serum albumin (second of two parts). N Engl J Med. 1976 Mar 4;294(10):526–531. doi: 10.1056/NEJM197603042941005. [DOI] [PubMed] [Google Scholar]
- Levy G., Yacobi A. Letter: Effect of plasma protein binding on elimination of warfarin. J Pharm Sci. 1974 May;63(5):805–806. doi: 10.1002/jps.2600630539. [DOI] [PubMed] [Google Scholar]
- Lunde P. K., Rane A., Yaffe S. J., Lund L., Sjöqvist F. Plasma protein binding of diphenylhydantoin in man. Interaction with other drugs and the effect of temperature and plasma dilution. Clin Pharmacol Ther. 1970 Nov-Dec;11(6):846–855. doi: 10.1002/cpt1970116846. [DOI] [PubMed] [Google Scholar]
- Odar-Cederlöf I., Borgå O. Kinetics of diphenylhydantoin in uraemic patients: consequences of decreased plasma protein binding. Eur J Clin Pharmacol. 1974;7(1):31–37. doi: 10.1007/BF00614387. [DOI] [PubMed] [Google Scholar]
- Olsen G. D., Bennett W. M., Porter G. A. Morphine and phenytoin binding to plasma proteins in renal and hepatic failure. Clin Pharmacol Ther. 1975 Jun;17(6):677–684. doi: 10.1002/cpt1975176677. [DOI] [PubMed] [Google Scholar]
- Rane A., Lunde P. K., Jalling B., Yaffe S. J., Sjöqvist F. Plasma protein binding of diphenylhydantoin in normal and hyperbilirubinemic infants. J Pediatr. 1971 May;78(5):877–882. doi: 10.1016/s0022-3476(71)80369-4. [DOI] [PubMed] [Google Scholar]
- Reidenberg M. M., Affrime M. Influence of disease on binding of drugs to plasma proteins. Ann N Y Acad Sci. 1973 Nov 26;226:115–126. doi: 10.1111/j.1749-6632.1973.tb20474.x. [DOI] [PubMed] [Google Scholar]
- Reidenberg M. M., Odar-Cederlöf I., von Bahr C., Borgå O., Sjöqvist F. Protein binding of diphenylhydantoin and desmethylimipramine in plasma from patients with poor renal function. N Engl J Med. 1971 Jul 29;285(5):264–267. doi: 10.1056/NEJM197107292850506. [DOI] [PubMed] [Google Scholar]
- Schobben F., van der Kleijn E., Gabreëls F. J. Pharmacokinetics of di-n-propylacetate in epileptic patients. Eur J Clin Pharmacol. 1975 Feb 28;8(2):97–105. doi: 10.1007/BF00561557. [DOI] [PubMed] [Google Scholar]
- Schoenemann P. T., Yesair D. W., Coffey J. J., Bullock F. J. Pharmacokinetic consequences of plasma protein binding of drugs. Ann N Y Acad Sci. 1973 Nov 26;226:162–171. doi: 10.1111/j.1749-6632.1973.tb20479.x. [DOI] [PubMed] [Google Scholar]
- Shoeman D. W., Azarnoff D. L. The alteration of plasma proteins in uremia as reflected in their ability to bind digitoxin and diphenylhydantoin. Pharmacology. 1972;7(3):169–177. doi: 10.1159/000136286. [DOI] [PubMed] [Google Scholar]
- Simon D., Penry J. K. Sodium di-N-propylacetate (DPA) in the treatment of epilepsy. A review. Epilepsia. 1975 Nov;16(4):549–573. doi: 10.1111/j.1528-1157.1975.tb04738.x. [DOI] [PubMed] [Google Scholar]
