Summary
The in vivo serum protein binding characteristics of carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-E) were assessed in sera from 23 paediatric patients on CBZ monotherapy. We assumed that CBZ and CBZ-E binding to serum proteins comprised specific binding sites on α1-acid glycoprotein (AAG) and non-specific binding sites on serum albumin. Therefore, the binding characteristics of each compound were analysed according to specific and nonspecific binding equations.
Association constants for drug-AAG binding were 0.096 l·μmol−1 for CBZ and 0.023 l·μmol−1 for CBZ-E. Within the concentration ranges investigated the specific binding of each compound contributes to the drug-serum protein interactions. Age did not show a significant correlation with the serum unbound fraction of each compound.
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References
Mackichan JJ, Zola EM (1984) Determination of carbamazepine and carbamazepine 10, 11-epoxide binding to serum protein, albumin and α1-acid glycoprotein. Br J Clin Pharmacol 18: 487–493
Eadie MJ (1991) Formation of active metabolites of anticonvulsant drugs: a review of their pharmacokinetic and therapeutic significance. Clin Pharmacokinet 21: 27–41
Contin M, Riva R, Albani F, Perucca E, Lamontanara G, Baruzzi A (1985) Alpha1-acid glycoprotein concentration and serum protein binding of carbamazepine and carbamazepine-10, 11 epoxide in children with epilepsy. Eur J Clin Pharmacol 29: 211–214
Müller WE (1985) A common single binding site for many psychotropic drugs on human α1-acid glycoprotein: therapeutically relevant observation? Pharmacopsychiatry 18: 257–258
Piafsky KM (1980) Disease-induced change in the plasma binding of basic drugs. Clin Pharmacokinet 5: 246–262
Bertilsson L, Tomson T, Tybring G (1986) Pharmacokinetics: time-dependent changes — autoinduction of carbamazepine epoxidation. J Clin Pharmacol 26: 459–462
Contin M, Riva R, Albani F, Perucca E, Baruzzi A (1985) Determination of total and free plasma carbamazepine concentrations by enzyme multiplied immunoassay: interference with the 10, 11-epoxide metabolite. Ther Drug Monit 7: 46–50
Levy RH, Friel PN, Johno I, Linthicum LM, Colin L, Koch K, Raisys VA, Wilensky AJ, Temkin NR (1984) Filtration for free drug level monitoring: carbamazepine and valproic acid. Ther Drug Monit 6: 67–76
Yamaoka K, Tanigawara Y, Nakagawa T, Uno T (1981) A pharmacokinetic analysis program (MULTI) for microcomputer. J Pharmacobiodyn 4: 879–885
Sheiner LB, Beal SL (1981) Some suggestions for measuring predictive performance. J Pharmacokinet Biopharm 9: 503–512
Vaughan VC III, Mckay RJ, Behrman RE (1979) Nelson: textbook of pediatrics. Saunders, Philadelphia
Lerman J, Strong HA, Ledez KM, Swartz J, Rieder MJ, Burrows FA (1989) Effects of age on the serum concentration of α1-acid glycoprotein and the binding of lidocaine in pediatric patients. Clin Pharmacol Ther 46: 219–225
Riva R, Contin M, Albani F, Baruzzi A (1985) High α1-acid glycoprotein concentrations in serum of epileptic children being treated with carbamazepine. Clin Chem 31: 150–151
Svensson CK, Woodruff MN, Lalka D (1986) Influence of protein binding and use of unbound (free) drug concentrations. In: Evans WE, Schentag JJ, Jusko WJ (eds) Applied pharmacokinetics: principles of therapeutic drug monitoring. Applied Therapeutic, Spokane
Svensson CK, Woodruff MN, Baxter JG, Lalka D (1986) Free concentration monitoring in clinical practice: rationale and current status. Clin Pharmacokinet 11: 450–469
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Kodama, Y., Tsutsumi, K., Kuranari, M. et al. In vivo binding characteristics of carbamazepine and carbamazepine-10, 11-epoxide to serum proteins in paediatric patients with epilepsy. Eur J Clin Pharmacol 44, 291–293 (1993). https://doi.org/10.1007/BF00271375
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DOI: https://doi.org/10.1007/BF00271375