Репозиторий Университета

© 2018 Elsevier B.V. Resistance to antiepileptic drugs (AEDs) is a major clinical problem. The overexpression of P-glycoprotein (Pgp), one of the main transporters limiting the entry of xenobiotics into the brain, is among the factors contributing to the AED resistance. Presently, there is no consensus on the interaction of carbamazepine (CBZ) with the Pgp. This study investigates the effect of the Pgp inhibitor verapamil on the anticonvulsant effect of CBZ and its nanoparticulate formulation in the rat model of isoniazid-induced epilepsy. Verapamil significantly increased the anticonvulsant effect of CBZ and reduced its effective dose by at least 30% (from 30 mg/kg to 20 mg/kg). Binding of carbamazepine to the poloxamer 188-coated PLGA nanoparticles enabled a 30-fold increase of its anticonvulsive effect, as compared to the free drug. The inhibition of Pgp did not influence the effectivity of carbamazepine encapsulated in nanoparticles.

© 2018, Media Sphera Publishing Group. All rights reserved. Aim — the study purpose was to analyze the efficacy of intra-arterial administration of verapamil (IAV) in the treatment of angiospasm in SAH patients and to determine optimal parameters of the procedure. A number of studies demonstrated the efficacy of intra-arterial administration of vasodilators, in particular verapamil, in the treatment of angiospasm after aneurysmal SAH, which served the basis for inclusion of this method in the recommended protocol for treatment of SAH patients [1―7]. Material and methods. We analyzed the efficacy of IAV in 35 patients in the acute period of SAH, with 77.2% of the patients having a Hunt-Hess score of III―V. The inclusion criteria were as follows: IAV within two weeks after SAH; excluded aneurysm; verapamil dose per administration of at least 15 mg; follow-up for at least three months. Efficacy endpoints were as follows: changes in spasm according to angiography and transcranial dopplerography (TCDG); development of ischemic lesions; clinical outcome according to the modified Rankin scale. Results. A total of 76 IAV procedures were performed. The verapamil dose per procedure was 36.7±9.7 mg, on average; the number of procedures varied from 1 to 5. One arterial territory was treated in 12 cases, two arterial territories were treated in 48 cases, and three arterial territories were treated in 15 cases. Typical adverse reactions included decreased blood pressure, a reduced heart rate, and elevated ICP. In all cases, TCDG revealed signs of reduced angiospasm ― a 20―40% decrease in the LBFV in the M1 MCA. Four (11.4%) patients died; of these, only one died due to angiospasm progression. On examination at 3 months or more after discharge, favorable outcomes were observed in 74.3% of cases. Conclusion. IAV is associated with a low risk of significant complications. IAV should be performed under control of systemic hemodynamics and ICP. The indications for IAV include signs of moderate worsening or severe angiospasm according to TCDG and/or angiography. The IAV procedure may be performed every day. Further clarification of the IAV procedure and evaluation of clinical outcomes under prospective study conditions are required.