BACKGROUND: Effective oral loading of carbamazepine (CBZ) is very important as it is the most often administered drug for partial and generalized seizures. The pharmacokinetics and tolerability of a single oral loading of controlled-release form of carbamazepine (CBZ-CR) were assessed in 38 adult patients at risk for seizure. METHODS: CBZ-CR was administered to 38 adults (22 had had CBZ just before entry into the study and 16 had not) at a dosage of 20 mg/kg as a single loading. Side effects and serum levels of CBZ and CBZ-10,11-epoxide (CBZ-E) were evaluated at 0, 2, 4, 6, 8, 12, 18, 24 h after the loading. Correlations between the frequency of side effects and other parameters (maxium serum concentration : Cmax, time to maximum concentration Tmax and area under the concentration time curve (AUC) of CBZ and CBZ-E) were also assessed. RESULTS: Mean CBZ serum levels (percentage of subjects with level > 4 Mg/ml shown in parenthesis) were 0.0 (0%), 3.2 (30%), 6.1 (79%), 7.2 (92%), 7.7 (95%), 7.7 (95%), 7.7 (95%) and 7.1 Mg/ml (95%) at 0, 2, 4, 6, 8, 12, 18 and 24 h after loading. Cmax and Tmax were 8.42 Mg/ml and 13.2 h respective-ly. Although side effects developed in 15 patients (39%), there were no significant neurotoxic side effects. The frequen-cy of the history of CBZ use was not different (p<0.05) in the two groups (one had side effects, another had not). Cmax, Tmax, and AUC of CBZ and CBZ-E were also not different (p<0.05). CONCLUSIONS: A single oral loading dose of CBZ-CR provides therapeutic serum concentrations quickly (in most patients within 6h) and is well tolerated. Rapid loading with CBZ-CR appears to be a useful alternative for the management of patients with a high risk of seizures.
Adult ; Anticonvulsants ; Area Under Curve ; Carbamazepine* ; Humans ; Pharmacokinetics ; Seizures

The prognosis of epilepsy has improved considerably, and about 80% of patients can now be expected to achieve complete seizure control with antiepileptic drug treatment. It is important to understand that the response to individual drugs may vary considerably in relation to the seizure type or epilepsy syndrome, so that optimization of treatment requires careful individualization of the dosage, and that rational polytherapy should be performed in consideration of the mechanisms of action of antiepileptic drugs, adverse effects, and drug interactions. Although newly developed antiepileptic drugs have some advantages in terms of adverse effects and pharmacokinetics compared with traditional antiepileptic drugs, they have demonstrated no significant difference in efficacy in comparative studies. The purpose of this chapter is to review the basic principles, which should guide the optimal treatment with antiepileptic drugs in patients with epilepsy.
Anticonvulsants ; Drug Interactions ; Epilepsy* ; Humans ; Pharmacokinetics ; Prognosis ; Seizures

OBJECTIVETo establish a population pharmacokinetics (PPK) model of lamotrigine, an antiepileptic drug, in Chinese children with epilepsy to formulate an individualized dosage guideline.

METHODSA total of 303 data, including the random ones of serum lamotrigine concentrations from 165 epileptic children were analyzed. Lamotrigine concentrations were determined by the RP-HPLC method. PPK model of lamotrigine was established using NONMEM, a population pharmacokinetic computer program, according to one-compartment model with first-order absorption and elimination. To evaluate the accuracy and precision of predicting lamotrigine concentrations, mean error (ME), mean squared prediction error (MSE), standard mean squared prediction error (SME), root mean squared prediction error (RSME), WRES and their 95% confidence interval were calculated in both the base and the final models.

RESULTSRegression equation of the base model of lamotrigine was obtained, ie, clearance (CL/F)=0.664 X EXP[ETA(1)], volume of distribution (V/F)=45 X EXP[ETA(2)], and KA=4.0 X EXP [ETA(3)], and that of the final model was as follows: CL/F=0.717 X (1-0.601 X VPA) X (1+1.18 X EI) X [1.62 lambda(AGE/7.02)] X EXP[ETA(1)], V/F=40.2 X EXP[ETA(2)], KA=3.27 X EXP [ETA(3)]. The population values of CL/F, V/F and KA were 1.16 L/h (0.042 L/h/kg), 40.2 L(1.46 L/kg) and 3.27/h for lamotrigine respectively in the final model. The final PPK model was demonstrated to be stable and effective in the prediction of serum lamotrigine concentrations by internal and external approaches validation.

CONCLUSIONSA PPK model of lamotrigine in Chinese children with epilepsy was successfully established using NONMEM. Lamotrigine concentrations can be predicted accurately by the model. The model may be helpful to reasonable use of antiepileptic drugs in clinical practice.

Adolescent ; Anticonvulsants ; pharmacokinetics ; Child ; Child, Preschool ; Epilepsy ; drug therapy ; metabolism ; Female ; Humans ; Infant ; Male ; Models, Biological ; Triazines ; pharmacokinetics

No abstract available.
Animal ; Animal Welfare ; Anticonvulsants/*pharmacology ; Drug Design ; Drug Interactions ; Epilepsy/*drug therapy ; Human ; Mice ; Pharmacokinetics ; Rats

Status epilepticus and refractory status epilepticus represent some of the most complex conditions encountered in the neurological intensive care unit. Challenges in management are common as treatment options become limited and prolonged hospital courses are accompanied by complications and worsening patient outcomes. Antiepileptic drug treatments have become increasingly complex. Rational polytherapy should consider the pharmacodynamics and kinetics of medications. When seizures cannot be controlled with medical therapy, alternative treatments, including early surgical evaluation can be considered; however, evidence is limited. This review provides a brief overview of status epilepticus, and a recent update on the management of refractory status epilepticus based on evidence from the literature, evidence-based guidelines, and experiences at our institution.
Anticonvulsants ; Complementary Therapies ; Critical Care ; Humans ; Intensive Care Units ; Kinetics ; Pharmacokinetics ; Seizures ; Status Epilepticus*

Status epilepticus and refractory status epilepticus represent some of the most complex conditions encountered in the neurological intensive care unit. Challenges in management are common as treatment options become limited and prolonged hospital courses are accompanied by complications and worsening patient outcomes. Antiepileptic drug treatments have become increasingly complex. Rational polytherapy should consider the pharmacodynamics and kinetics of medications. When seizures cannot be controlled with medical therapy, alternative treatments, including early surgical evaluation can be considered; however, evidence is limited. This review provides a brief overview of status epilepticus, and a recent update on the management of refractory status epilepticus based on evidence from the literature, evidence-based guidelines, and experiences at our institution.
Anticonvulsants ; Complementary Therapies ; Critical Care ; Humans ; Intensive Care Units ; Kinetics ; Pharmacokinetics ; Seizures ; Status Epilepticus

PURPOSE: The pharmacokinetics of phenytoin is complicated by genetic and environmental differences. It is, therefore, important to monitor the serum concentrations in patients who receive phenytoin. Because most of the phenytoin in serum is bound to proteins, the level of serum albumin influences the amount of free phenytoin. MATERIALS AND METHODS: We compared the measured and calculated free phenytoin levels in epileptic patients who were taking phenytoin monotherapy, using the Sheiner-Tozer equation. A total of 49 patients (30 men and 19 women; age range, 15 - 87 years) were included in the study and their trough serum phenytoin and albumin concentrations were analyzed. RESULTS: The linear correlation between free and total phenytoin concentrations was moderate (r = 0.822, p < 0.001). The mean difference between measured and calculated free phenytoin was large (0.65 +/- 0.88 microg/mL; 95% confidence interval (CI), -1.11 to 2.41). After dividing the patients into groups by albumin concentration, hypoalbuminemic patients (< 3.5 g/dL) more often had a greater percent difference (> or = 20%) than observed in the normoalbuminemic (> or = 3.5 g/dL) group. CONCLUSION: In hypoalbuminemic patients, the measurement of free phenytoin level is necessary to properly evaluate the phenytoin level than that calculated from total phenytoin level.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anticonvulsants/*blood/pharmacokinetics/therapeutic use ; Epilepsy/*blood/drug therapy ; Female ; Humans ; Male ; Middle Aged ; Phenytoin/*blood/pharmacokinetics/therapeutic use ; Young Adult

OBJECTIVE: To study the relation between human blood estazolam concentration and neurobehavioral function. METHODS: The neurobehavioral ability of 10 volunteers were measured with computer-administered neurobehavioral evaluation system-chinese3 (NES-C3) and SMART EquiTest system. RESULTS: The neurobehavioral ability and balance function declined 1 h later after dosing estazolam. The neurobehavioral ability index and balance function declined to the lowest level 3 h later after dosing estazolam. The neurobehavioral ability recovered partly 6 h later after dosing estazolam, and neurobehavioral ability recovered completely 10 h later. CONCLUSION Driving ability was impaired when estazolam concentration in blood is 20 ng/mL, and the neurobehavioral ability declined when estazolam concentration is 40 ng/mL in blood. The influence to human in absorption process is greater than the metabolic process with the same estazolam concentration.
Accidents, Traffic/prevention & control* ; Administration, Oral ; Adult ; Anticonvulsants/pharmacokinetics* ; Attention/drug effects* ; Behavior/drug effects* ; Estazolam/pharmacokinetics* ; Female ; Humans ; Male ; Neuropsychological Tests ; Psychomotor Performance/drug effects* ; Reaction Time

To investigate the effects of carbamazepine (CBZ) on the plasma concentrations of valproic acid (VPA) and its toxic metabolite 2-propyl-4-pentenoic acid (4-ene VPA) in epileptic patients, the plasma concentrations of VPA and 4-ene VPA were determined, and the effect of CBZ on pharmacokinetics of VPA was evaluated. All patients had been divided into two groups (VPA group, n = 87; and VPA+CBZ group, n = 19). As compared to VPA group, the combination of CBZ significantly (P < 0.01) decreased the trough concentration of VPA [VPA group, (69.5 +/- 28.8) microg x mL(-1); VPA+CBZ group, (46.3 +/- 25.6) microg x mL(-1)] and does-adjusted VPA trough concentration [VPA group, (4.89 +/- 2.21) microg x mL(-1) x mg(-1) x kg(-1); VPA+CBZ group, (3.14 +/- 1.74) microg x mL(-1) x mg(-1) x kg(-1)]. However, the addition of CBZ did not influence the concentration of 4-ene VPA. The present study revealed that coadministration of CBZ can reduce VPA plasma concentration and may impact VPA clinical effect, therefore therapeutic drug mornitoring of VPA should be used when combined use of CBZ and VPA.
Adolescent ; Adult ; Anticonvulsants ; blood ; pharmacokinetics ; therapeutic use ; Carbamazepine ; blood ; pharmacokinetics ; therapeutic use ; Drug Interactions ; Drug Therapy, Combination ; Epilepsy ; blood ; drug therapy ; Fatty Acids, Monounsaturated ; blood ; Female ; Humans ; Male ; Valproic Acid ; blood ; pharmacokinetics ; therapeutic use ; Young Adult

The use of antiepileptic drugs in pregnancy always presents challenges to doctors and their patients as it may have deleterious effects on the developing embryo. Lamotrigine is most commonly-prescribed drug among the newer antiepileptic drugs; hence, it has been selected for the present review. A number of studies pertaining to the safety of lamotrigine use during pregnancy have been reported, with differing results. Contradictory results have been reported in animals regarding lamotrigine teratogenicity, and human studies have also proven inconclusive. In many countries, human pregnancy registries are maintained to establish the safety of antiepileptic drugs during pregnancy, as all the different suggestions favour some over others, with specific antiepileptic combinations still being questioned. It is our hope that the present work may integrate the available disparate relevant facts into a directed effort towards minimising the risk of foetal compromise.
Abnormalities, Drug-Induced ; Animals ; Anticonvulsants ; adverse effects ; therapeutic use ; Epilepsy ; drug therapy ; Female ; Folic Acid Deficiency ; chemically induced ; Humans ; Pregnancy ; Teratogens ; pharmacokinetics ; pharmacology ; Triazines ; adverse effects ; therapeutic use