Background: Post-traumatic seizures are a medical problem affecting patients with traumatic brain injury. Yet effective treatment is lacking owing to the limitations of anti-epileptic drugs (AEDs) applicable to these patients. Method: In this study, we evaluated the dose-response efficacy of levetiracetam (12.5-100.0mg/kg) and gabapentin (1.25-25.0mg/kg) administered either individually or in pairs at fixed-dose ratios as a combination in mitigating post-traumatic nonconvulsive seizures induced by severe penetrating ballistic-like brain injury (PBBI) in rats. Seizures were detected by continuous EEG monitoring for 72h post-injury. Animals were treated twice per day for 3 days by intravenous injections. Results: Both levetiracetam (25-100mg/kg) and gabapentin (6.25-25mg/kg) significantly reduced PBBI-induced seizure frequency by 44-73% and 61-69%, and seizure duration by 45-64% and 70-78%, respectively. However the two drugs manifested different dose-response profiles. Levetiracetam attenuated seizure activity in a dose-dependent fashion, whereas the beneficial effects of gabapentin plateaued across the 3 highest doses tested. Combined administration of levetiracetam and gabapentin mirrored the more classic dose-response profile of levetiracetam monotherapy. However, no additional benefit was derived from the addition of gabapentin. Furthermore, isobolicgraphic analysis of the combination dose-response profile of levetiracetam and gabapentin failed to reach the expected level of additivity, suggesting an unlikelihood of favorable interactions between these two drugs against spontaneously occurring post-traumatic seizure activities at the particular set of dose ratios tested. Discussion: This study was the first attempt to apply isobolographic approach to studying AED combination therapy in the context of spontaneously occurring post-traumatic seizures. Despite the failure to achieve additivity from levetiracetam and gabapentin combination, it is important to recognize the objectivity of the isobolographic approach in the evaluation of AED combination therapy in the context of seizures directly associated with brain injuries. (C) 2017 Lippincott Williams & Wilkins, Inc.
from Emergency Medicine via xlomafota13 on Inoreader http://ift.tt/2pHtEzv
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
[PDF] Καρκίνος του στομάχου -- Αλέξανδρος Γ. Σφακιανάκης Αναπαύσεως 5 Άγιος Νικόλαος Λασιθίου 72100 2841026182
-
Abstract Introduction In recent years, platelet-rich plasma (PRP) has emerged as a promising autologous biological treatment modality fo...
-
P2Y2 Nucleotide Receptor Is a Regulator of the Formation of Cardiac Adipose Tissue and Its Fat-Associated Lymphoid Clusters P2Y2 Nucleotide ...
-
Rehab patients are friends and co-workers, which requires additional awareness for rehab medical personnel and preplanning to administer ove...
-
Tales from the Night:: Emergency MR Imaging in Pediatric Patients after Hours Publication date: May 2019 Source: Magnetic Resonance Imaging...
-
blood bank stuff: The basics of crit care transfusion medicine EMCrit by Scott Weingart . from Emergency Medicine via xlomafota13 on I...
-
DELAYED RESPONSE: It is yet another delayed ambulance response to an emergency in D.C. With no ambulance in sight, a man suffering from mult...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου