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European Journal of Clinical Pharmacology

, Volume 32, Issue 3, pp 321–323 | Cite as

Effects of josamycin on carbamazepine kinetics

  • G. Vinçon
  • H. Albin
  • F. Demotes-Mainard
  • M. Guyot
  • C. Bistue
  • P. Loiseau
Short Communications

Summary

The steady state pharmacokinetics of oral carbamazepine in epileptic patients (n=8) was compared before and after one week of treatment with josamycin (2 g/day). There was a small but statistically significant decrease in oral clearance of total (17%) and unbound (21.5%) drug. In spite of an unchanged AUC of 10,11-epoxide carbamazepine the ratio of metabolite to parent drug AUC was significantly decreased (20.2%). The plasma protein binding of carbamazepine and its 10,11-epoxide metabolite did not vary. The results demonstrate impairment by josamycin of the apparent clearance of carbamazepine. Care should be taken in patient receiving both carbamazepine and josamycin.

Key words

carbamazepine josamycin drug interaction epileptic patients pharmacokinetics 

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References

  1. 1.
    Albin H, Vinçon G, Pehourcq F, Dangoumau J (1982) Influence de la josamycine sur la pharmacocinétique de la carbamazépine. Therapie 37: 151–156Google Scholar
  2. 2.
    Bigorie B, Aimez P, Soria RJ, Samama F, Dimaria G, Guy-Grand B, Bour H (1975) L'association triacétyloléandomycine-tartrate d'ergotamine est-elle dangereuse? Nouv Presse Med 4: 2723–2725Google Scholar
  3. 3.
    Brazier JL, Kofman J, Faucon G, Perin-Fayolle M, Lepape A, Lanque R (1980) Retard d'élimination de la théophylline dû à la troléandomycine. Absence d'effet de la josamycine. Therapie 35: 545–549Google Scholar
  4. 4.
    Dravet C, Mesdjian E, Cenraud B, Roger J (1977) Interaction carbamazépine-troléandomycine: une nouvelle interaction médicamenteuse? Nouv Presse Med 6: 567–569Google Scholar
  5. 5.
    Eichelbaum M, Bertilsson L (1975) Determination of carbamazepine and its epoxide metabolite in plasma by high speed liquid chromatography. J Chromatrogr 103: 135–140Google Scholar
  6. 6.
    Eichelbaum M, Tomson T, Tybring G, Bertilsson L (1985) Carbamazepine metabolism in man. Induction and pharmacogenetic aspects. Clin Pharmacokinet 10: 80–90Google Scholar
  7. 7.
    Faigle JW, Feldman KF (1982) Carbamazepine biotransformation. In: Woodburry EM, Penry JK, Pipenger CE (eds) Antiepileptic drugs (2nd edn). Raven Press, New YorkGoogle Scholar
  8. 8.
    Hayton AC (1969) Precipitation of acute ergotism by triacetyloleandomycin. NZ Med J 69: 42–43Google Scholar
  9. 9.
    Hooper WD, Dubetz DK, Bochner F, Cotter LM, South GA, Eadie MJ, Tyrer JM (1975) Plasma protein binding of carbamazepine. Clin Pharmacol Ther 17: 433–440Google Scholar
  10. 10.
    Larrey D, Funck-Brentano C, Breil P, Vitaux J, Theodore C, Babany G, Pessayre D (1983) Effects of erythromycin on hepatic drug-metabolizing enzymes in humans. Biochem Pharmacol 32: 1063–1068Google Scholar
  11. 11.
    Levy RM, Pitlick WH, Troupin AS, Green JR, Neal JM (1975) Pharmacokinetics of carbamazepine in normal man. Clin Pharmacol Ther 17: 657–668Google Scholar
  12. 12.
    Mesdjian E, Dravet C, Cenraud B, Roger J (1980) Carbamazepine intoxication due to triacetyloleandomycin administration in epileptic patients. Epilepsia 21: 489–496Google Scholar
  13. 13.
    Pynnönen S, Sillanpää M, Frey H, Iisola E (1977) Carbamazepine and its 10,11-epoxide in children and adults with epilepsy. Eur J Clin Pharmacol 11: 129–133Google Scholar
  14. 14.
    Riva R, Contin M, Albani F, Perucca E, Ambrosetto G, Gobbi G, Cortelli P, Procaccianti G, Baruzzi A (1984) Free and total plasma concentrations of carbamazepine and carbamazepine-10,11-epoxide in epileptic patients: Diurnal fluctuations and relationship with side-effects. Ther Drug Monit 6: 408–413Google Scholar
  15. 15.
    Rowland M, Tozer TN (1980) Clinical pharmacokinetics: Concepts and applications. Lea & Febiger, PhiladelphiaGoogle Scholar
  16. 16.
    Webster LK, Mihaly GW, Jones DB, Smallwood RA, Phillips JA, Vajda FJ (1984) Effects of cimetidine and ranitidine on carbamazepine and sodium valproate pharmacokinetics. Eur J Clin Pharmacol 27: 341–343Google Scholar
  17. 17.
    Weinberger M, Hudgel D, Spector S, Chidsey C (1977) Inhibition of theophylline clearance by troleandomycin. J Allergy Clin Immunol 59: 228–231Google Scholar
  18. 18.
    Westenberg HGM, Van der Kleijn E, Oei TT, de Zeeuw R (1978) Kinetics of carbamazepine and carbamazepine-epoxide determined by use of plasma and saliva. Clin Pharmacol Ther 23: 320–328Google Scholar
  19. 19.
    Wilkinson GR, Shand DG (1975) A physiological approach to hepatic drug clearance. Clin Pharmacol Ther 18: 377–390Google Scholar
  20. 20.
    Wong YY, Ludden TM, Bell RD (1983) Effect of erythromycin on carbamazepine kinetics. Clin Pharmacol Ther 33: 460–464Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • G. Vinçon
    • 1
  • H. Albin
    • 1
  • F. Demotes-Mainard
    • 1
  • M. Guyot
    • 2
  • C. Bistue
    • 1
  • P. Loiseau
    • 2
  1. 1.Department of Clinical PharmacologyHôpital PellegrinBordeauxFrance
  2. 2.Department of NeurologyHôpital PellegrinBordeauxFrance

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