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0044 Levetiracetam: Relative bioavailability and bioequivalence of 10% oral solution (750 mg) and 750 mg tablets
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Monday, November 7, 2005
seven. His seizures are characterized by head version to the right followed by the secondarily generalized tonic clonic seizures. [nterictal EEG spike focus was localized in the left frontal region, however, MRI showed post-traumatic lesionsin the left parietal and tempo ral area. Intracranial recording confirmed the seizure onset left prefrontal area. Surgical disconnection of epileptogenic area eliminated the seizures for 1 year. Conclusion: Epilepsy surgery with subdural grid electrode evaluation is effective for the treatment of post-traumatic epilepsy. The epileptogenic focus may be located away form the lesions shovat by the imaging studies. 0043 Levetixaeetaln in Refractory Epflepw: 2 ~ years of experience AI-Jishi, A. Sabnaniya Medical Complex
A Retrospective analysis of twenty patients (eleven males and nine females) from Bahrain with Refractory Epilepsy seen between September 2002 and March 2005. Age ranged between 18-45 years. These patients were put on Levetiracetam(LEV) as add-on therapy. Duration of Epilepsy was 4-30 years. There were 6 generalized epilepsies and 14 partial with or without secondary generalization. There were 16 symptomatic or cryptogenic epilepsies and 4 idiopathic epilepsies. Average of 4 drugs were tried before addition of LEV and 2 concomitant drugs after the addition of LEV. Results: No benefit in 3 patients (15%), < 50% seizures reduction in 3 patients (15%), > 50',/0 seizures reduction in 14 patients (70%) and 100% control in 2 patients (10%). Side Elleels: Were minor and occurred in 40% of patients and one withdrew LEV for fear of pregnancy. Conclusion: LEV proved to be highly effective and safe in majority of Refractory Epilepsy. 0044 Levetixaeetam: Relative Bioavailability and Bioequivalence of 10% Oral Solution (750 mg) and 750 mg Tablets
Coupez, R ~, Straetemans, R ~, Sehgal, G ~, Stoclds, A ~, Lu, Z ~.
~UCB S.A. Pharma Sector, Chemin du Yoriest, Braine l'Alleu& Belgium; 2UCB Pharma Inc., Smyrna, Georgia, USA Purpose: Levetiracetam (LEV) is widely used as adjunctive treatment for partial-onset seizures. The availability o f a LEV oral solution formulation would provide an additional treatment option for patients with difficulty swallowing tablets. This study evaluated the bioequivalence of 10% LEV oral solution compared to 750 mg oral tablet and characterised its pharmacokinetics. Methods: A phase I single-centre, randomised, open-label, two-way crossover, single-dose study was conducted. Each of 24 healthy subjects received a single oral 750 mg dose of the randomised LEV formulation (7.5 mL 10% solution or 750 mg table 0 on Day 1 and a single oral dose of the alternate fommlation on Day 8. Serial blood samples were collected from 0 to 36 hours after each dosing for determination of plasma LEV concentrations. Pharmacokinetic parameters were calculated and bioeqnivalence of the two formulations evaluated. Results: The mean LEV plasma concentration time curves and pharmacokinetic parameters were essentially identical for the oral 10% solution and 750 mg tablet and consistent with previously reported LEV pharmacokinetics. 90% confidence limits of the geometric mean ratio of the two formulations for area under the plasma concentration-time curve from time 0 to infinity, area under the plasma concentration-rime curve from time 0 to last measurable time point, and maximum plasma concentration were within the 80% to 125',/o range, demonstrating bioequivalence of the two formulations. Both formulations were well tolerated.
Poster Abstracts Contusions: The LEV 10% oral solution is a bioequivalent, well tolerated alternative to the tablet formulation in patients who have difficulty swallowing.
0045 Early Posit-Stroke Seizures Treated with Levefiracetam Daniele O ~, Didato G ~, Fierro B ~, Vind G 2, Tata M R 3, Natal~ E 2.
1Department of N. O.O.P., University of Palermo, Palermo, Italy; 2Department of Neurosciences, Ospedale Civico, ARNAS, Palermo, Italy; 3Department of Neurosciences, University of Napoli, Napoli, Italy Purpose: In the elderly, ischaemic or haemorrhagic stroke is one of the most common causes of seizures or epilepsy. Early post-stroke seizures (ES) occur immediately after, or witlffn 15 days of the stroke (up to 80"/0 of patients wiffiin 48 hours), and are regarded as a risk factor for seizure recurrence. According to most authors ES are easy to control, requiring only antiepileptie drug (AED) monotherapy. We evaluated the effect of Leveriracetam (LEV), a new AED with a pharmacokinetic profile close to ideal, as monotherapy in the treatment of ES. Methods: 54 patients with ES were included in the study. 34 patients (20 male, 14 female); mean age 73 years received LEV (29 with ischaemic, 5 with haemorrhagic stroke) and 20 (all with ischaemic stroke) were controls. Focal seizures occurred in 13 patients (11 with ischaemic and 2 with haemorrhagic stroke); in 10 patients, lesions were located in cortical regions and in 8 a secondary generalisation occurred. Generalised seizures occurred in 21 patients (18 with ischaemic and 3 with haemor,-hagic stroke). LEV was administered at doses of 1500-3000 mg/daily with low titration, for a 6-monffi period and a follow-up to-date of 12 months. Results: Seizure recurrence was observed in only 2 (5.8%) of the 34 LEV-treated patients whereas they recurred in 3 (115%) of the 20 controls. Only 3 (18.8"/o) patients complained o f mild somnolence. Conclusions: On the basis of tiffs study, LEV should be considered as a useful and safe drug in the treatment of ES.
0046 Levetiracetam in the Treatment of Idiopathic Generalised Seizures NatalS, E*, Fierro, B2, Didato, G 2, Brighina, F 2, Tata, M 3, Daniele, 0 2.
1Department of Neuroseiences, Ospedale Civico, ARNAS, Palermo, Italy; 2Department of N.O.O.P., University of Palermo, Palermo, Italy; :Department of Neuroseienees, University of Napoli, Napoli, Italy Purpose: Levetiracetam (LEV) is approved as add-on therapy in patients wiffi refractory partial onset seizures. Increasing evidence suggest its efficacy in primary generalised seizures. We evaluated the efficacy of LEV as both add-on and monoffierapy in patients wiffi primary generalised epilepsies. Methods: Nineteen (19) patients (111 male, 8 female); mean age 23 (range 9-32) years with generalised epilepsies were included in the study: 4 Absence, 8 Juvenile Myoclonic Epilepsy (JME) and 7 Generalised Tonic-Clonic ( G T Q seizures. At study entry antiepileptic drug (AED) therapy included VPA (11), VPA + LTG (4), VPA + PB (1), PB (2), and LTG (1), and all patients were still experiendng monthly seizures. Patients received LEV 1500-4000 mg/daily initially as add-on therapy, and are gradually being converted to LEV monotherapy (lover a 3 month period). Maximum follow-up to date (the study is still ongoing) is 18 months. Results: All 19 patients improved both clinically and electroencephalographically after LEV initiation with a _>50% seizure frequency reduction. Currently, 3 JME and 2 GTC patients have received LEV monotherapy for 12 months, all 5 (100%) patients are seizure-free since 6-12 months. Of the remaining 14 patients still receiving LEV add-on therapy 9 (165"/o) achieved seizure freedom for 6-12 months and 5 (35%) had a 50-75"/0 seizure frequency reduction. Only 3 patients experienced mild somnolence, not requiring LEV discontinuation.
Monday, November 7, 2005
seven. His seizures are characterized by head version to the right followed by the secondarily generalized tonic clonic seizures. [nterictal EEG spike focus was localized in the left frontal region, however, MRI showed post-traumatic lesionsin the left parietal and tempo ral area. Intracranial recording confirmed the seizure onset left prefrontal area. Surgical disconnection of epileptogenic area eliminated the seizures for 1 year. Conclusion: Epilepsy surgery with subdural grid electrode evaluation is effective for the treatment of post-traumatic epilepsy. The epileptogenic focus may be located away form the lesions shovat by the imaging studies. 0043 Levetixaeetaln in Refractory Epflepw: 2 ~ years of experience AI-Jishi, A. Sabnaniya Medical Complex
A Retrospective analysis of twenty patients (eleven males and nine females) from Bahrain with Refractory Epilepsy seen between September 2002 and March 2005. Age ranged between 18-45 years. These patients were put on Levetiracetam(LEV) as add-on therapy. Duration of Epilepsy was 4-30 years. There were 6 generalized epilepsies and 14 partial with or without secondary generalization. There were 16 symptomatic or cryptogenic epilepsies and 4 idiopathic epilepsies. Average of 4 drugs were tried before addition of LEV and 2 concomitant drugs after the addition of LEV. Results: No benefit in 3 patients (15%), < 50% seizures reduction in 3 patients (15%), > 50',/0 seizures reduction in 14 patients (70%) and 100% control in 2 patients (10%). Side Elleels: Were minor and occurred in 40% of patients and one withdrew LEV for fear of pregnancy. Conclusion: LEV proved to be highly effective and safe in majority of Refractory Epilepsy. 0044 Levetixaeetam: Relative Bioavailability and Bioequivalence of 10% Oral Solution (750 mg) and 750 mg Tablets
Coupez, R ~, Straetemans, R ~, Sehgal, G ~, Stoclds, A ~, Lu, Z ~.
~UCB S.A. Pharma Sector, Chemin du Yoriest, Braine l'Alleu& Belgium; 2UCB Pharma Inc., Smyrna, Georgia, USA Purpose: Levetiracetam (LEV) is widely used as adjunctive treatment for partial-onset seizures. The availability o f a LEV oral solution formulation would provide an additional treatment option for patients with difficulty swallowing tablets. This study evaluated the bioequivalence of 10% LEV oral solution compared to 750 mg oral tablet and characterised its pharmacokinetics. Methods: A phase I single-centre, randomised, open-label, two-way crossover, single-dose study was conducted. Each of 24 healthy subjects received a single oral 750 mg dose of the randomised LEV formulation (7.5 mL 10% solution or 750 mg table 0 on Day 1 and a single oral dose of the alternate fommlation on Day 8. Serial blood samples were collected from 0 to 36 hours after each dosing for determination of plasma LEV concentrations. Pharmacokinetic parameters were calculated and bioeqnivalence of the two formulations evaluated. Results: The mean LEV plasma concentration time curves and pharmacokinetic parameters were essentially identical for the oral 10% solution and 750 mg tablet and consistent with previously reported LEV pharmacokinetics. 90% confidence limits of the geometric mean ratio of the two formulations for area under the plasma concentration-time curve from time 0 to infinity, area under the plasma concentration-rime curve from time 0 to last measurable time point, and maximum plasma concentration were within the 80% to 125',/o range, demonstrating bioequivalence of the two formulations. Both formulations were well tolerated.
Poster Abstracts Contusions: The LEV 10% oral solution is a bioequivalent, well tolerated alternative to the tablet formulation in patients who have difficulty swallowing.
0045 Early Posit-Stroke Seizures Treated with Levefiracetam Daniele O ~, Didato G ~, Fierro B ~, Vind G 2, Tata M R 3, Natal~ E 2.
1Department of N. O.O.P., University of Palermo, Palermo, Italy; 2Department of Neurosciences, Ospedale Civico, ARNAS, Palermo, Italy; 3Department of Neurosciences, University of Napoli, Napoli, Italy Purpose: In the elderly, ischaemic or haemorrhagic stroke is one of the most common causes of seizures or epilepsy. Early post-stroke seizures (ES) occur immediately after, or witlffn 15 days of the stroke (up to 80"/0 of patients wiffiin 48 hours), and are regarded as a risk factor for seizure recurrence. According to most authors ES are easy to control, requiring only antiepileptie drug (AED) monotherapy. We evaluated the effect of Leveriracetam (LEV), a new AED with a pharmacokinetic profile close to ideal, as monotherapy in the treatment of ES. Methods: 54 patients with ES were included in the study. 34 patients (20 male, 14 female); mean age 73 years received LEV (29 with ischaemic, 5 with haemorrhagic stroke) and 20 (all with ischaemic stroke) were controls. Focal seizures occurred in 13 patients (11 with ischaemic and 2 with haemorrhagic stroke); in 10 patients, lesions were located in cortical regions and in 8 a secondary generalisation occurred. Generalised seizures occurred in 21 patients (18 with ischaemic and 3 with haemor,-hagic stroke). LEV was administered at doses of 1500-3000 mg/daily with low titration, for a 6-monffi period and a follow-up to-date of 12 months. Results: Seizure recurrence was observed in only 2 (5.8%) of the 34 LEV-treated patients whereas they recurred in 3 (115%) of the 20 controls. Only 3 (18.8"/o) patients complained o f mild somnolence. Conclusions: On the basis of tiffs study, LEV should be considered as a useful and safe drug in the treatment of ES.
0046 Levetiracetam in the Treatment of Idiopathic Generalised Seizures NatalS, E*, Fierro, B2, Didato, G 2, Brighina, F 2, Tata, M 3, Daniele, 0 2.
1Department of Neuroseiences, Ospedale Civico, ARNAS, Palermo, Italy; 2Department of N.O.O.P., University of Palermo, Palermo, Italy; :Department of Neuroseienees, University of Napoli, Napoli, Italy Purpose: Levetiracetam (LEV) is approved as add-on therapy in patients wiffi refractory partial onset seizures. Increasing evidence suggest its efficacy in primary generalised seizures. We evaluated the efficacy of LEV as both add-on and monoffierapy in patients wiffi primary generalised epilepsies. Methods: Nineteen (19) patients (111 male, 8 female); mean age 23 (range 9-32) years with generalised epilepsies were included in the study: 4 Absence, 8 Juvenile Myoclonic Epilepsy (JME) and 7 Generalised Tonic-Clonic ( G T Q seizures. At study entry antiepileptic drug (AED) therapy included VPA (11), VPA + LTG (4), VPA + PB (1), PB (2), and LTG (1), and all patients were still experiendng monthly seizures. Patients received LEV 1500-4000 mg/daily initially as add-on therapy, and are gradually being converted to LEV monotherapy (lover a 3 month period). Maximum follow-up to date (the study is still ongoing) is 18 months. Results: All 19 patients improved both clinically and electroencephalographically after LEV initiation with a _>50% seizure frequency reduction. Currently, 3 JME and 2 GTC patients have received LEV monotherapy for 12 months, all 5 (100%) patients are seizure-free since 6-12 months. Of the remaining 14 patients still receiving LEV add-on therapy 9 (165"/o) achieved seizure freedom for 6-12 months and 5 (35%) had a 50-75"/0 seizure frequency reduction. Only 3 patients experienced mild somnolence, not requiring LEV discontinuation.