Carbamazepine kinetics in cardiac patients before and during amiodarone

Leite, Silmara A.O.; Leite, Paulo J.M.; Rocha, Gilberto A.; Routledge, Philip A.; Bittencourt, Paulo Rogério M.

doi:10.1590/S0004-282X1994000200010

Abstracts

Carbamazepine and amiodarone may often be used together, especially in countries where cardiomyopathies are common. In this study single doses of carbamazepine (400 mg) were given to patients with cardiac disease before and after one month of therapy with amiodarone, 400 mg daily. The kinetic profile of carbamazepine, its free fraction, and serum amiodarone, were measured at the two occasions. There was no statistically significant change in carbamazepine kinetics or free fraction, before and after the introduction of amiodarone. The concentrations of amidarone after one month of therapy were low. It is sugested that the possible interaction in the hepatic metabolism was not demonstrated because amiodarone concentrations were not enough to inhibit carbamazepine metabolism.

amiodarone; carbamazepine; epilepsy; antiepileptic drags; arrythmia

Carbamazepina e amiodarona podem frequentemente ser usadas em conjunto, especialmente em países em que as cardiomiopatias são comuns. Neste estudo doses de carbamazepina (400 mg) foram administradas a pacientes com doenças cardíacas antes e depois de um mês de terapia com amiodarona, 400 mg ao dia. O perfil cinético da carbamazepina, sua fração livre e o nível sérico da amiodarona, foram avaliados nas duas ocasiões. Não foram observadas diferenças estatisticamente significantes na cinética da carbamazepina ou mesmo em sua fração livre, antes e depois da introdução da amiodarona. A concentração da amiodarona após um mês de terapia foi baixa. Conclui-se que a possível interação no metabolismo hepático não foi demonstrada devido as baixas concentrações de amiodarona, que provavelmente tenham sido insuficientes para inibir o metabolismo da carbamazepina.

amiodarona; carbamazepina; drogas antiepilépticas; arritmias

Carbamazepine kinetics in cardiac patients before and during amiodarone

Cinética da carbamazepina em pacientes cardíacos antes e durante amiodarona

Silmara A.O. Leite^I; Paulo J.M. Leite^I; Gilberto A. Rocha^II; Philip A. Routledge^III; Paulo Rogério M. Bittencourt^I

^IServiço de Neurologia, Hospital Nossa Senhora das Graças, Curitiba, Brasil

^IIServiço de Cardiologia, Hospital Nossa Senhora das Graças, Curitiba, Brasil

^IIIDepartamento de Farmacologia e Terapêutica, Universidade de País de Gales, Faculdade de Medicina, Heath Park, Cardiff, País de Gales

SUMMARY

Carbamazepine and amiodarone may often be used together, especially in countries where cardiomyopathies are common. In this study single doses of carbamazepine (400 mg) were given to patients with cardiac disease before and after one month of therapy with amiodarone, 400 mg daily. The kinetic profile of carbamazepine, its free fraction, and serum amiodarone, were measured at the two occasions. There was no statistically significant change in carbamazepine kinetics or free fraction, before and after the introduction of amiodarone. The concentrations of amidarone after one month of therapy were low. It is sugested that the possible interaction in the hepatic metabolism was not demonstrated because amiodarone concentrations were not enough to inhibit carbamazepine metabolism.

Key words: amiodarone, carbamazepine, epilepsy, antiepileptic drags, arrythmia.

RESUMO

Carbamazepina e amiodarona podem frequentemente ser usadas em conjunto, especialmente em países em que as cardiomiopatias são comuns. Neste estudo doses de carbamazepina (400 mg) foram administradas a pacientes com doenças cardíacas antes e depois de um mês de terapia com amiodarona, 400 mg ao dia. O perfil cinético da carbamazepina, sua fração livre e o nível sérico da amiodarona, foram avaliados nas duas ocasiões. Não foram observadas diferenças estatisticamente significantes na cinética da carbamazepina ou mesmo em sua fração livre, antes e depois da introdução da amiodarona. A concentração da amiodarona após um mês de terapia foi baixa. Conclui-se que a possível interação no metabolismo hepático não foi demonstrada devido as baixas concentrações de amiodarona, que provavelmente tenham sido insuficientes para inibir o metabolismo da carbamazepina.

Palavras chave: amiodarona, carbamazepina, drogas antiepilépticas, arritmias.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

Acknowledgement - The authors would like to thank nursing staff at Hospital N.S. das Graças in Curitiba for their cooperation, and Ms Maristela G. Calderari and Ms Marli Osna for word processing. The study was supported by an internal grants of the Unidade de Neurologia Clínica S/C, Curitiba and of the Department of Pharmacology and Therapeutics, University of Wales College of Medicine.

Aceite: 4-novembro-1993.

Dr. Paulo R.M. de Bittencourt - Unidade de Neurologia Clínica, Hospital Nossa Senhora das Graças - Rua Alcides Munhoz 433 - 80810-040 Curitiba PR - Brasil.

1. Adams RF, Vandermark FL. Simultaneous high pressure liquid chromatrographic determination of some anticonvulsivants in serum. Clin Chem 1976, 22:25-31.
2. Andreasen F, Agerback H, Byerregaard P, Gotzche H. Pharmacokinetics of amiodarone after intravenous and oral administration. J Clin Pharmacol 1981,19:293-299.
3. Bittencourt PRM. Epilepsy in Latin America. In Laidlaw J, Richens A, Oxley J (eds). Textbook of epilepsy. Edinburgh: Churchill-Livingstone 1988, p 518-528.
4. Bittencourt PRM, Gracia CM, Lorenzana P. Epilepsy and parasitosis of the central nervous system. In Pedley T, Meldrum B (eds). Recent advances in epilepsy, Vol 4. Edinburgh: Churchill-Livingstone, 1988, p 123-161.
5. Bittencourt PRM, Perucca E, Crema A. Cerebellar toxicity of antiepileptic drugs. In Blum K, Manzo L (eds). Neurotoxicology, drug and chemical toxicology. London: Marcel Dekker, 1985, p 233-250.
6. Bittencourt PRM, Richens A. Assessment of antiepileptic drug toxicity by eye movements. In Buser PA, Cobb WA, Okuma T (eds). Kyoto Symposia (EEG Suppl 36). Amsterdam: Elsevier, 1982, p.467-481.
7. Bittencourt PRM, Richens A. Concentrações séricas eficazes após doses únicas de drogas antiepilépticas: conceito de dose-carga. Arq Neuropsiquiatr, 1985, 43:11 -16.
8. Dalton MJ, Powell JR. Messenheimer JA Jr. The influence of Cimetidine on single dose carbamazepine pharmacokinetics. Epilepsia 1985, 26 (Suppl): 127-130.
9. Haffajee CL, Love JC, Canda AT, Lesko LJ, Asdourian G, Alpert JS. Clinical pharmacokinetics and efficacy of amiodarone for refractory tachyarrhythmias. Circulation 1983,67:1347-1355.
10. Holt WD, Tucker GT, JacksonPR, Story GCA. Amiodarone pharmacokinetics. Am Heart J, 1983,106:840-847.
11. Hutchings A, Spragg B, Routledge PA. High performance liquid chromatographic assay of amiodarone and desethylamiodarone in plasma. J Chromatogr, 1986, 382:389-393.
12. Latini R, Tognoni G, Kates RE. Clinical pharmacokinetics of amiodarone. Clin Pharmacokin 1984, 9:136-156.
13. Leite PJM, Tsanaclis LM, Markourakis T, Bittencourt PRM. Dose carga de carbamazepina e difenil-hidantoina: Utilização em pacientes de alto risco. Arq Neuropsiquiatr 1987, 45:281-287.
14. Mason WJ. Drug therapy: amiodarone. N Eng J Med 1987, 19:455-465.
15. Morselli PL. Carbamazepine: absorption, distribution and excretion. In Levy RH, Dreifuss FE, Mattson RH, Meldrum BS, Penry JK (eds). Antiepileptic drugs. Ed 3. New York: Raven Press 1989, p 473-491.
16. Perucca E, Bittencourt PRM, Richens A. Effect of dose increments on serum carbamazepine concentration in epileptic patients. Clin Pharmacokin 1980, 5:576-582.
17. Plomp TA, van Rossum JM, van Lie T, Maes RAA. Pharmacokinetics and body distribution of amiodarone in man. Arzneimittelforsch 1984, 34:513-520.
18. Siddoway AL, McAllister CB, Wilkinson GR, Roden DM, Woosley RL. Amiodarone dosing: a proposal based on its pharmacokinetics. Am Heart J 1983, 106:951-956.
19. Watt AH. Stephens MR, Buss DC, Routledge PA. Amiodarone reduces plasma warfarin clearance in man. Br J Clin Pharmacol 1985, 20:707-709.

Publication Dates

Publication in this collection
19 Jan 2011
Date of issue
June 1994

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Adams RF, Vandermark FL. Simultaneous high pressure liquid chromatrographic determination of some anticonvulsivants in serum. Clin Chem 1976, 22:25-31.

[2] 2. Andreasen F, Agerback H, Byerregaard P, Gotzche H. Pharmacokinetics of amiodarone after intravenous and oral administration. J Clin Pharmacol 1981,19:293-299.

[3] 3. Bittencourt PRM. Epilepsy in Latin America. In Laidlaw J, Richens A, Oxley J (eds). Textbook of epilepsy. Edinburgh: Churchill-Livingstone 1988, p 518-528.

[4] 4. Bittencourt PRM, Gracia CM, Lorenzana P. Epilepsy and parasitosis of the central nervous system. In Pedley T, Meldrum B (eds). Recent advances in epilepsy, Vol 4. Edinburgh: Churchill-Livingstone, 1988, p 123-161.

[5] 5. Bittencourt PRM, Perucca E, Crema A. Cerebellar toxicity of antiepileptic drugs. In Blum K, Manzo L (eds). Neurotoxicology, drug and chemical toxicology. London: Marcel Dekker, 1985, p 233-250.

[6] 6. Bittencourt PRM, Richens A. Assessment of antiepileptic drug toxicity by eye movements. In Buser PA, Cobb WA, Okuma T (eds). Kyoto Symposia (EEG Suppl 36). Amsterdam: Elsevier, 1982, p.467-481.

[7] 7. Bittencourt PRM, Richens A. Concentrações séricas eficazes após doses únicas de drogas antiepilépticas: conceito de dose-carga. Arq Neuropsiquiatr, 1985, 43:11 -16.

[8] 8. Dalton MJ, Powell JR. Messenheimer JA Jr. The influence of Cimetidine on single dose carbamazepine pharmacokinetics. Epilepsia 1985, 26 (Suppl): 127-130.

[9] 9. Haffajee CL, Love JC, Canda AT, Lesko LJ, Asdourian G, Alpert JS. Clinical pharmacokinetics and efficacy of amiodarone for refractory tachyarrhythmias. Circulation 1983,67:1347-1355.

[10] 10. Holt WD, Tucker GT, JacksonPR, Story GCA. Amiodarone pharmacokinetics. Am Heart J, 1983,106:840-847.

[11] 11. Hutchings A, Spragg B, Routledge PA. High performance liquid chromatographic assay of amiodarone and desethylamiodarone in plasma. J Chromatogr, 1986, 382:389-393.

[12] 12. Latini R, Tognoni G, Kates RE. Clinical pharmacokinetics of amiodarone. Clin Pharmacokin 1984, 9:136-156.

[13] 13. Leite PJM, Tsanaclis LM, Markourakis T, Bittencourt PRM. Dose carga de carbamazepina e difenil-hidantoina: Utilização em pacientes de alto risco. Arq Neuropsiquiatr 1987, 45:281-287.

[14] 14. Mason WJ. Drug therapy: amiodarone. N Eng J Med 1987, 19:455-465.

[15] 15. Morselli PL. Carbamazepine: absorption, distribution and excretion. In Levy RH, Dreifuss FE, Mattson RH, Meldrum BS, Penry JK (eds). Antiepileptic drugs. Ed 3. New York: Raven Press 1989, p 473-491.

[16] 16. Perucca E, Bittencourt PRM, Richens A. Effect of dose increments on serum carbamazepine concentration in epileptic patients. Clin Pharmacokin 1980, 5:576-582.

[17] 17. Plomp TA, van Rossum JM, van Lie T, Maes RAA. Pharmacokinetics and body distribution of amiodarone in man. Arzneimittelforsch 1984, 34:513-520.

[18] 18. Siddoway AL, McAllister CB, Wilkinson GR, Roden DM, Woosley RL. Amiodarone dosing: a proposal based on its pharmacokinetics. Am Heart J 1983, 106:951-956.

[19] 19. Watt AH. Stephens MR, Buss DC, Routledge PA. Amiodarone reduces plasma warfarin clearance in man. Br J Clin Pharmacol 1985, 20:707-709.