ABSTRACT
To assess changes in the pharmacokinetics of the anti-epileptic drug lamotrigine (LTG) during pregnancy, plasma LTG concentrations at steady-state were determined at different intervals during 11 pregnancies in 10 women with epilepsy stabilized on long-term LTG therapy. In the five pregnancies that could be assessed both during gestation and after delivery, plasma LTG concentrations increased on average by 164% (range +75 to +351%) between the last observation during pregnancy and the puerperium (P < 0.05). When all pregnancies monitored during pregnancy were considered, plasma LTG concentrations declined by an average of 20% (range -64% to +13%) between the first and the last assessment before delivery. These findings confirm that plasma LTG concentrations decrease markedly during pregnancy and that, at least in some cases, this effect occurs as early as the first trimester. Because there is a large interindividual variability in the magnitude and time course of the pregnancy-associated pharmacokinetic changes, it is desirable to establish baseline plasma LTG concentrations in all women of childbearing potential and to monitor LTG levels at frequent intervals during pregnancy and the puerperium.
Subject(s)
Anticonvulsants/pharmacokinetics , Postpartum Period/metabolism , Pregnancy/metabolism , Triazines/pharmacokinetics , Adult , Anticonvulsants/administration & dosage , Calibration , Chromatography, High Pressure Liquid , Drug Interactions , Female , Humans , Lamotrigine , Triazines/administration & dosage , Young AdultABSTRACT
PURPOSE: The kindling model in rats with genetic absence epilepsy is suitable for studying mechanisms involved in the propagation and generalization of seizure activity in the convulsive and nonconvulsive components of epilepsy. In the present study, we compared the amygdala kindling rate and afterdischarge characteristics of the nonepileptic Wistar control rat with a well-validated model of absence epilepsy, the WAG/Rij rat, and demonstrated the effect of amygdala kindling on spike-and-wave discharges (SWDs) in the WAG/Rij group. METHODS: Electrodes were stereotaxically implanted into the basolateral amygdala of rats for stimulation and recording and into the cortex for recording. After a recovery period, the animals were stimulated at their afterdischarge thresholds. EEG was recorded to analyze SWDs and afterdischarge durations. The seizure severity was evaluated by using Racine's 5-stage scale. RESULTS: All nonepileptic control and four of seven WAG/Rij animals reached a stage 5 seizure state, whereas three animals failed to reach stage 3, 4, or 5 and stayed at stage 2 after application of 30 stimulations. Interestingly, WAG/Rij rats, resistant to kindling, demonstrated a significantly longer duration of SWDs on the first day of the experiment before kindling stimulation than did the kindled WAG/Rij animals. Additionally, the cumulative total duration and the number of SWDs after the kindling stimulation were statistically increased compared with SWDs before kindling stimulation. CONCLUSIONS: The results of our study demonstrate that the progress of amygdala kindling is changed in rats with genetic absence epilepsy, perhaps as a consequence of the hundreds of daily SWDs.
Subject(s)
Amygdala/physiology , Electroencephalography/statistics & numerical data , Epilepsy, Absence/physiopathology , Kindling, Neurologic/physiology , Animals , Brain Mapping , Cerebral Cortex/physiopathology , Disease Models, Animal , Electric Stimulation , Electrodes, Implanted , Electroencephalography/methods , Epilepsy, Absence/diagnosis , Epilepsy, Absence/genetics , Functional Laterality/physiology , Limbic System/physiopathology , Rats , Rats, Inbred Strains , Rats, Wistar , Severity of Illness Index , Stereotaxic TechniquesABSTRACT
PURPOSE: This study was planned to investigate the baroreflex responses (BRs) in kindled rats during seizure-free period to put forward new data on cardiac autonomic changes in epilepsy. METHODS: Male Wistar rats were randomized into sham-operated (SO) and kindled groups where stimulation and recording electrodes were implanted stereotaxically into the basolateral amygdala and the cortex, respectively. For kindling process, rats were stimulated twice daily at their afterdischarge threshold current and accepted as being kindled after 10 grade 5 seizures. Six to 8 weeks after the establishment of the kindled state, mean arterial pressure (MAP) and heart rate (HR) were evaluated. BR was defined as the ratio of HR response to changes in MAP induced by i.v. nitroprusside (10, 25 microg/kg) or i.v. phenylephrine (10, 25 microg/kg). The sympathetic or parasympathetic component of the BR was evaluated in rats pretreated with atropine or atenolol where phenylephrine or nitroprusside was administered at 25 microg/kg. RESULTS: Basal MAP and HR values were found to be similar in SO and kindled rats. Phenylephrine increased MAP more in the kindled group (p < 0.05), but the HR decreased similarly in both groups. Nitroprusside decreased MAP at similar rates, but the increase in HR was higher in the kindled rats (p < 0.05). BRs to phenylephrine and nitroprusside were abolished after pretreatment with atenolol and atropine, whereas phenylephrine- and nitroprusside-induced changes in MAP remained unchanged in both groups. CONCLUSIONS: These results may indicate that amygdaloid kindling affects BRs in long-term seizure-free periods.
