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

Bittencourt, P. R. M.; Richens, A.

doi:10.1590/s0004-282x1985000100002

Cited by 4 publications

(2 citation statements)

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“…Studies of effective acute oral loading doses of phenytoin (PHT, Wilder et al, 1973;Gibberd and Webley, 1975;Evens et al, 1980;Bittencourt and Richens, 1985;Osborn et al, 1987;Leite et al, 1987;Galdames et al, 1988) (Table 1) and carbamazepine (CBZ, Schmidt et al, 1984;Bittencourt and Richens, 1985;Macphee et al, 1986;Leppik et al, 1988; Leite et al, 1987;Bourgeois et al, 1989;Miles et al, 1989, Van der Meyden et al, 1992) (Table 2) are sparse and incomplete.…”

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Acute Oral Loading of Carbamazepine‐CR and Phenytoin in a Double‐Blind Randomized Study of Patients at Risk of Seizures

et al. 1994

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The serum levels and side effects of an acute oral loading dose-schedule of carbamazepine (CBZ) divitabs [CBZ controlled release (CR)] and phenytoin (PHT) were assessed in patients at risk of seizures. CBZ-CR and PHT were administered to 42 adult patients (21 each) at a dosage of 20 mg/kg with a minimum and maximum dosage of 1,200 and 1,600 mg in patients weighting < 60 and > 80 kg, respectively. CBZ-CR was given as single loading dose; PHT was split, with two thirds of the dose administered at 0 h and one third administered 2 h later. The 24- and 36-h doses were assessed according to the nystagmus status at 24 h. Mean CBZ serum levels (percentage of subjects with level > 4 micrograms/ml shown in parentheses) were 0.0 (0%), 5.2 (62%), 6.7 (81%), 6.8 (95%), and 6.1 micrograms/ml (95%) at 0, 4, 8, 24, and 48 h after loading, respectively, and mean PHT levels (percentage of subjects with PHT level > 10 micrograms/ml in parentheses) were 0.1 (0%), 13.2 (86%), 16.3 (100%), 16.3 (100%), and 15.4 micrograms/ml (82%). One subject in the CBZ group and 3 in the PHT group vomited. Clinical effects did not differ significantly between treatment groups and are reported. Acute doses of CBZ-CR 20 mg/kg and PHT 20 mg/kg (two-thirds at 0 h and one-third at 2 h) provided therapeutic levels in most patients in < or = 4 h and were well tolerated.

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Acute Oral Loading of Carbamazepine‐CR and Phenytoin in a Double‐Blind Randomized Study of Patients at Risk of Seizures

et al. 1994

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“…Assim, existe variação inter-indi¬ vidual de níveis séricos na administração não só de drogas antiepilépticas 3,19, como em várias outras, incluindo antibióticos e digoxina 19 . A partir da evidência de uma boa correlação entre níveis séricos de várias drogas antiepilépticas e grau de controle das crises 8,19,20,23 , chegou-se ao conceito de faixa terapêutica, válida estatisticamente para a maioria da população 19. Para a carbamazepina a faixa terapêutica é considerada de 4,8 a 11,9mg/ml e para a difenil-hidantoína de 10 a 25/mg/ml 9 .…”

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Doses-carga de carbamazepina e difenil-hidantoína: utilização em pacientes de alto risco

Leite

Tsanaclis

Markourakis

et al. 1987

Arq. Neuro-Psiquiatr.

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Loading-doses of phenytoin (1000 mg) and carbamazepine (600 mg) were given orally respectively to 10 and 6 patients with uncontrolled epileptic seizures secondary to acute neurological disorders or alcohol withdrawal. In the phenytoin group age varied between 12-73 years and serum concentrations at 2, 4, 6, 8, 12 and 18 hours after drug administration were 7.6, 8.8, 8.7, 8.7, 7.2 and 6.5 micrograms/ml (means). A quantitative method did not detect important side-effects. In the carbamazepine group age varied between 25-56 years and serum concentrations at the same times were 3.9, 5.3, 6.5, 7.5, 7.4 and 8.2 micrograms/ml. Side-effects were discrete. Further medication was not necessary in the 24 hours after drug administration. Although both regimens controlled the clinical situation without relevant side-effects serum concentrations were sub-therapeutic in the case of phenytoin. We suggest the ideal phenytoin oral loading-dose is 1500 mg. The carbamazepine load produced therapeutic concentrations. The stability of serum concentrations for the period of the study shows that those regimens are useful in the subacute control of epileptic seizures in the maintenance treatment of status epilepticus and in alcohol withdrawal.

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IV Valproate in generalized convulsive status epilepticus: a systematic review

Brigo

Storti

Felice

et al. 2011

Euro J of Neurology

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Aim of this review was to evaluate efficacy and safety of intravenous valproate (IV VPA) in the treatment of generalized convulsive status epilepticus (GCSE) in patients of any age, synthesizing available evidences from randomized controlled trials (RCTs). RCTs on IV VPA administered in patients (no age restriction) for GCSE at any stage were searched in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials. Studies were selected and data independently extracted. Following outcomes were considered: clinical seizure cessation after drug administration, seizure freedom at 24 h, and adverse effects. Outcomes were assessed using standard methods to calculate risk ratio (RR) with 95% confidence intervals. Five trials met inclusion criteria. Two different comparisons were available (IV VPA versus phenytoin (PHT), IV VPA versus IV Diazepam), but only the former included more than one study with enough information to permit a meta-analysis. Compared with PHT, VPA had statistically lower risk of adverse effects (RR 0.31, 95% CI 0.12-0.85), with no differences in GCSE cessation after drug administration (RR 1.31, 95% CI 0.93-1.84) and in seizure freedom at 24 h (RR 0.96, 95% CI 0.88-1.06). This review suggests that IV VPA has a better tolerability than PHT in treatment of GCSE, without any statistically significant differences in terms of efficacy. More rigorous RCTs of VPA versus an appropriate comparator, in a well-defined population with a systematic definition of SE, are however required to conclude about efficacy and tolerability of VPA in clinical practice.

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

Cited by 4 publications

References 10 publications

Acute Oral Loading of Carbamazepine‐CR and Phenytoin in a Double‐Blind Randomized Study of Patients at Risk of Seizures

Acute Oral Loading of Carbamazepine‐CR and Phenytoin in a Double‐Blind Randomized Study of Patients at Risk of Seizures

Doses-carga de carbamazepina e difenil-hidantoína: utilização em pacientes de alto risco

IV Valproate in generalized convulsive status epilepticus: a systematic review

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