Concentrações séricas eficazes após doses únicas de drogas anti-epiléticas: conceito de dose carga

Bittencourt, Paulo R.M.; Richens, Alan

doi:10.1590/S0004-282X1985000100002

Resumos

Doses únicas de fenitoína (500 a l.OOOmg), carbamazepina (400 e l.OOOmg) e valproato de sódio (600mg) foram administradas oralmente a 5 voluntários normais jovens e concentrações séricas foram determinadas entre 1 e 8 horas após administração. A técnica foi duplo-cega, controlada por placebo. Concentrações séricas "terapêuticas" foram obtidas após valproato de sódio e após a dose de l.OOOmg de carbamazepina. Os resultados sugerem que doses-carga de fenitoína (1.500-2.000mg) e carbamazepina (800mg) são úteis no controle sub-agudo de crises epilépticas freqüentes em pacientes de ambulatório e que carbamazepina pode ser utilizada para o controle crônico de estado de mal epiléptico inicialmente tratado com diazepam ou outra preparação de ação rápida.

Single doses of phenytoin (500 and l.OOOmg), carbamazepine (400 and l.OOOmg) and sodium valproate (600mg) were given orally to 5 healthy young volunteers and serum concentrations determined between l-8h after administration. The design was double-blind and placebo-controlled. Serum concentrations considered "therapeutic" were obtained after sodium valproate and the lOOOmg dose of carbamazepine. The results suggest the loading-doses of phenytoin (1500-2000mg) and carbamazepine (800mg) are useful in the subacute control of frequent epileptic seizures on an out-patient basis, and that carbamazepine may be used for lasting control of seizures of status epilepticus treated initially with diazepam or other rapidly-acting preparation.

Concentrações séricas eficazes após doses únicas de drogas anti-epiléticas: conceito de dose carga

Efficient serum concentrations after single doses of antiepileptic drugs: the loading-dose concept

Paulo R.M. Bittencourt^I; Alan Richens^II

^IAmbulatório de Epilepsia, Hospital de Clinicas da Universidade Federal do Paraná e Unidade de Neurologia, Hospital Nossa Senhora das Graças, Curitiba, Brasil

^IIDepartment of Pharmacology and Therapeutics, Welsh National School of Medicine, Cardiff, País de Gales, UK

RESUMO

Doses únicas de fenitoína (500 a l.OOOmg), carbamazepina (400 e l.OOOmg) e valproato de sódio (600mg) foram administradas oralmente a 5 voluntários normais jovens e concentrações séricas foram determinadas entre 1 e 8 horas após administração. A técnica foi duplo-cega, controlada por placebo. Concentrações séricas "terapêuticas" foram obtidas após valproato de sódio e após a dose de l.OOOmg de carbamazepina. Os resultados sugerem que doses-carga de fenitoína (1.500-2.000mg) e carbamazepina (800mg) são úteis no controle sub-agudo de crises epilépticas freqüentes em pacientes de ambulatório e que carbamazepina pode ser utilizada para o controle crônico de estado de mal epiléptico inicialmente tratado com diazepam ou outra preparação de ação rápida.

SUMMARY

Single doses of phenytoin (500 and l.OOOmg), carbamazepine (400 and l.OOOmg) and sodium valproate (600mg) were given orally to 5 healthy young volunteers and serum concentrations determined between l-8h after administration. The design was double-blind and placebo-controlled. Serum concentrations considered "therapeutic" were obtained after sodium valproate and the lOOOmg dose of carbamazepine. The results suggest the loading-doses of phenytoin (1500-2000mg) and carbamazepine (800mg) are useful in the subacute control of frequent epileptic seizures on an out-patient basis, and that carbamazepine may be used for lasting control of seizures of status epilepticus treated initially with diazepam or other rapidly-acting preparation.

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Unidade de Neurologia, Departamento de Clinica Médica, Hospital Nossa Senhora das Graças - Rua Alcides Munhoz, 433, Mercês - 80000, Curitiba, PR - Brasil.

1. BITTENCOURT, P.R.M. - The effects of some centrally-acting drugs on saccadic and smooth pursuit eye movements in man. PhD Thesis, University of London. London, 1981, pg. 191.
2. BITTENCOURT, P.R.M. & DHILLON, S. - Benzodiazepines: clinical aspects. In A. Richens & V. Marks (eds.): Therapeutic Drug Monitoring. Churchill-Livingstone, Edinburgh, 1981, pg. 275.
3. BITTENCOURT, P.R.M.; GABARDO, A.C. & SILVADO, C.E.S. - Monotherapy without serum levels for epilepsy. Abstracts, 15th International Epilepsy Symposium, 1983, pg. 131.
4. BITTENCOURT, P.R.M. & RICHENS, A. - Assessment of antiepileptic drug toxicity by eye movements. In P.A. Buser, W.A. Cobb & T. Okuma (eds.): Kyoto Symposia (EEG Supplement 36). Elsevier Biomedical, Amsterdam, 1982, pg. 467.
5. DELGADO-ESCUETA, A.V.; WASTERLAIN, C; TREIMAN, D.M. & PORTER, R.J. - Current concepts in neurology: management of status epilepticus. New Engl. J. Med. 306:1337, 1982.
6. GRAM, L.; FLACHS, H.; WURTZ-JORGENSEN, A.; PARNAS, J. & ANDERSEN, B. - Sodium valproate, relationship between serum levels and therapeutic effect: a controlled study. In S.I. Johannessen et al (eds.): Antiepileptic Therapy: Advances in Drug Monitoring. Raven Press, New York, 1980, pg. 217.
7. GUGLER, R.; MANION, C.V. & AZERNOFF, D.L. - Phenytoin: pharmacokinetics and bio availability. Clin. Pharmac. Therap. 19:135, 1976.
8. HENRIKSEN, O. & JOHANNESSEN, S.I. - Clinical observations of sodium valproate in children: an evaluation of therapeutic serum levels. In S.I. Johannessen et al (eds.): Antiepileptic Therapy: Advances in Drug Monitoring. Raven Press, New York, 1980, pg. 253.
9. LUND, L. - Anticonvulsant effect of diphenylhydantoin relative to plasma levels: a prospective 3-year study in ambulant patients with generalized epileptic seizures. Arch. Neurol. (Chicago) 31:289, 1974.
10. MAYNERT, E.W. - Phenobarbital: absorption, distribution and excretion. In D.M. Woodbury, J.K. Penry & C.E. Pippinger (eds.): Antiepileptic Drugs. Raven Press, New York, 1982, pg. 309.
11. PERUCCA, E.; BITTENCOURT, P.R.M. & RICHENS, A. - Effects of dose-increments on serum carbamazepine increments in epileptic patients. Clin. Pharmacokin. 5:576. 1980.
12. PERUCCA, E. & RICHENS, A. - Reversal by phenytoin of carbamazepine-induced water intoxication: a pharmacokinetic interaction. J. Neurol. Neurosurg. Psychiat. 43:540, 1980.
13. REYNOLDS, E.H. & SHORVON, S.D. - Monotherapy or polytherapy for epilepsy? Epilepsia 22:1, 1981.
14. RICHENS, A. - Clinical pharmacokinetics of phenytoin. Clin. Pharmacokin. 4:153, 1979.
15. RICHENS, A. - Clinical pharmacology and medical treatment: part ona In J. Laidlaw & A. Richens (eds.): A Textbook of Epilepsy. Churchill-Livingstone, Edinburgh, 1982, pg. 292.
16. RICHENS, A. & BITTENCOURT, P.R.M. - Disturbed eye movements in the epileptic patient. Brit. J. clin. Practice suppl. 27:120, 1983.
17. ROWAN, A.J.; BENNIE, CD.; WARFIELD, C.A.; MEINARDI, H. & MEIJER, J.W.A. - The late effect of sodium valproate on the photoconvulsive response in man. Epilepsia 20:61, 1979.
18. WILSON, J.T.; HOJER, B.; RAEN, A. - Loading and conventional dose therapy with phenytoin in children: kynetic profile of parent drug and main metabolite in plasma. Clin. Pharmacol. Ther. 20:48, 1976.

Datas de Publicação

Publicação nesta coleção
13 Ago 2012
Data do Fascículo
Mar 1985

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[1] 1. BITTENCOURT, P.R.M. - The effects of some centrally-acting drugs on saccadic and smooth pursuit eye movements in man. PhD Thesis, University of London. London, 1981, pg. 191.

[2] 2. BITTENCOURT, P.R.M. & DHILLON, S. - Benzodiazepines: clinical aspects. In A. Richens & V. Marks (eds.): Therapeutic Drug Monitoring. Churchill-Livingstone, Edinburgh, 1981, pg. 275.

[3] 3. BITTENCOURT, P.R.M.; GABARDO, A.C. & SILVADO, C.E.S. - Monotherapy without serum levels for epilepsy. Abstracts, 15th International Epilepsy Symposium, 1983, pg. 131.

[4] 4. BITTENCOURT, P.R.M. & RICHENS, A. - Assessment of antiepileptic drug toxicity by eye movements. In P.A. Buser, W.A. Cobb & T. Okuma (eds.): Kyoto Symposia (EEG Supplement 36). Elsevier Biomedical, Amsterdam, 1982, pg. 467.

[5] 5. DELGADO-ESCUETA, A.V.; WASTERLAIN, C; TREIMAN, D.M. & PORTER, R.J. - Current concepts in neurology: management of status epilepticus. New Engl. J. Med. 306:1337, 1982.

[6] 6. GRAM, L.; FLACHS, H.; WURTZ-JORGENSEN, A.; PARNAS, J. & ANDERSEN, B. - Sodium valproate, relationship between serum levels and therapeutic effect: a controlled study. In S.I. Johannessen et al (eds.): Antiepileptic Therapy: Advances in Drug Monitoring. Raven Press, New York, 1980, pg. 217.

[7] 7. GUGLER, R.; MANION, C.V. & AZERNOFF, D.L. - Phenytoin: pharmacokinetics and bio availability. Clin. Pharmac. Therap. 19:135, 1976.

[8] 8. HENRIKSEN, O. & JOHANNESSEN, S.I. - Clinical observations of sodium valproate in children: an evaluation of therapeutic serum levels. In S.I. Johannessen et al (eds.): Antiepileptic Therapy: Advances in Drug Monitoring. Raven Press, New York, 1980, pg. 253.

[9] 9. LUND, L. - Anticonvulsant effect of diphenylhydantoin relative to plasma levels: a prospective 3-year study in ambulant patients with generalized epileptic seizures. Arch. Neurol. (Chicago) 31:289, 1974.

[10] 10. MAYNERT, E.W. - Phenobarbital: absorption, distribution and excretion. In D.M. Woodbury, J.K. Penry & C.E. Pippinger (eds.): Antiepileptic Drugs. Raven Press, New York, 1982, pg. 309.

[11] 11. PERUCCA, E.; BITTENCOURT, P.R.M. & RICHENS, A. - Effects of dose-increments on serum carbamazepine increments in epileptic patients. Clin. Pharmacokin. 5:576. 1980.

[12] 12. PERUCCA, E. & RICHENS, A. - Reversal by phenytoin of carbamazepine-induced water intoxication: a pharmacokinetic interaction. J. Neurol. Neurosurg. Psychiat. 43:540, 1980.

[13] 13. REYNOLDS, E.H. & SHORVON, S.D. - Monotherapy or polytherapy for epilepsy? Epilepsia 22:1, 1981.

[14] 14. RICHENS, A. - Clinical pharmacokinetics of phenytoin. Clin. Pharmacokin. 4:153, 1979.

[15] 15. RICHENS, A. - Clinical pharmacology and medical treatment: part ona In J. Laidlaw & A. Richens (eds.): A Textbook of Epilepsy. Churchill-Livingstone, Edinburgh, 1982, pg. 292.

[16] 16. RICHENS, A. & BITTENCOURT, P.R.M. - Disturbed eye movements in the epileptic patient. Brit. J. clin. Practice suppl. 27:120, 1983.

[17] 17. ROWAN, A.J.; BENNIE, CD.; WARFIELD, C.A.; MEINARDI, H. & MEIJER, J.W.A. - The late effect of sodium valproate on the photoconvulsive response in man. Epilepsia 20:61, 1979.

[18] 18. WILSON, J.T.; HOJER, B.; RAEN, A. - Loading and conventional dose therapy with phenytoin in children: kynetic profile of parent drug and main metabolite in plasma. Clin. Pharmacol. Ther. 20:48, 1976.