The relationship between the serum protein binding of carbamazepine (CBZ) and carbamazepine-10,11 epoxide (CBZ-E) and the concentration of α1-acid glycoprotein (AAG) and albumin (HSA) was examined in 39 CBZ-treated epileptic children aged 4 months to 12 years.
A significant inverse correlation was found between the free fraction of both compounds and serum AAG, even though changes in AAG concentration explained only part of the variation in binding. No correlation was found between the free fraction of CBZ and CBZ-E and HSA, probably due to the small intersubject variation in HSA concentration. In vitro experiments showed that both CBZ and CBZ-E were bound to HSA and to a lesser extent to AAG. At equivalent HSA concentrations, the binding of CBZ and its metabolite increased proportionately with increasing AAG concentration within the range occurring clinically.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Bertilsson L (1978) Clinical pharmacokinetics of carbamazepine. Clin Pharmacokinet 3: 128–143
Hooper WD, Dubetz F, Bochner F, Cotter LM, Smith GA, Eadie MJ, Tyrer JH (1975) Plasma protein binding of carbamazepine. Clin Pharmacol Ther 18: 433–440
Lawless LM, De Monaco HJ, Muido LR (1982) Protein binding of carbamazepine in epileptic patients. Neurology (NY) 32: 415–418
Riva R, Contin M, Albani F, Perucca E, Ambrosetto G, Procaccianti G, Santucci M, Baruzzi A. (1985) Lateral gaze nystagmus in carbamazepine treated epileptic patients: Correlation with total and free plasma concentrations of parent drug and its 10,11 epoxide metabolite. Ther Drug Monit (in press)
MacKichan JJ, Zola EM (1984) Determinants of carbamazepine and carbamazepine 10,11-epoxide binding to serum protein, albumin and α1-acid glycoprotein. Br J Clin Pharmacol 18: 487–493
DiSalle E, Pacifici GM, Morselli PL (1974) Studies on plasma protein binding of carbamazepine. Pharmacol Res Commun 6: 193–202
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
Paxton JW (1983) α1-acid glycoprotein and binding of basic drugs. Meth Find Exp Clin Pharmacol 5: 635–648
Piafsky KM, Borga O (1977) Plasma protein binding of basic drugs II. Importance of α1-acid glycoprotein for interindividual variations. Clin Pharmacol Ther 22: 545–549
Urien S, Albengres E, Zini R, Tillement JP (1982) Evidence for binding of certain acidic drugs to α1-acid glycoprotein. Biochem Pharmacol 31: 3687–3689
Israili ZH, El-Attar H (1983) Binding of some acidic drugs to α1-acid glycoprotein. Clin Pharmacol Ther 33: 255
Piafsky KM (1980) Disease-induced changes in the plasma binding of basic drugs. Clin Pharmacokinet 5: 246–262
Bai SA, Abramson FP (1982) Interactions of phenobarbital with propranolol in the dog. 1. Plasma protein binding. J Pharmacol Exp Ther 222: 589–594
Brinkschulte M, Breyer-Pfaff U (1982) Increased binding of desmethylimipramine in plasma of phenobarbital treated rats. Biochem Pharmacol 31: 1749–1752
Olsson R, Hellner L, Lindstedt G, Lundberg P-A, Teger-Nilsson A-C (1983) Plasma proteins in patients on long-term antiepileptic treatment. Clin Chem 29: 728–730
Routledge PA, Stargel WW, Finn AL, Barchowsky A, Shand DG (1981) Lignocaine disposition in blood in epilepsy. Br J Clin Pharmacol 12: 663–666
Tiula E, Neuvonen PJ (1982) Antiepileptic drugs and α1-acid glycoprotein. N Engl J Med 307: 1148
Riva R, Contin M, Albani F, Baruzzi A, Lamontanara G (1985) High α1-acid glycoprotein concentrations in serum of epileptic children treated with carbamazepine. Clin Chem 31: 150
Lohman JJHM, Markus FWHM, Costongs GMPJ, Hegtermans EPJMH, Hooymans PM (1984) Pitfalls in the determination of unbound carbamazepine concentrations in plasma. Pharmazeutisch Weekblad 6: 91–95
Behm HL, Wagner JG (1979) Errors in interpretation of data from equilibrium dialysis protein binding experiments. Res Commun Chem Pathol Pharmacol 26: 145–160
Cramer JA, Mattson GF, Collins JF, Browne TR, V.A. Epilepsy Cooperative Study Group (1984) Correlation between phenytoin and carbamazepine free fraction and serum albumin. Epilepsia 25: 674–675
Riva R, Albani F, Ambrosetto G, Contin M, Cortelli P, Perucca E, Baruzzi A (1984) Diurnal fluctuations in free and total steady-state plasma levels of carbamazepine and correlation with intermittent side effects. Epilepsia 25: 476–481
Piafsky KM, Mpamugo L (1981) Dependence of neonatal drug binding on α1-acid glycoprotein concentration. Clin Pharmacol Ther 29: 272
Wood M, Wood AJJ (1981) Changes in plasma drug binding and α1-acid glycoprotein in mother and newborn infant. Clin Pharmacol Ther 29: 522–526
Bienvenu J, Sann L, Bienvenu F, Lahet C, Divry P, Cotte J, Bethenod M (1981) Laser nephelometry orosomucoid in serum of newborns: Reference intervals and relation to bacterial infection. Clin Chem 27: 721–726
About this article
Cite this article
Contin, M., Riva, R., Albani, F. et al. 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 (1985). https://doi.org/10.1007/BF00547424
- carbamazepine-10,11 epoxide
- alpha1-acid glycoprotein
- serum protein binding