![]() Plasma Sample Preparation for Lacosamide Quantification. The plasma supernatant was stored at -70 ℃ prior to analysis. All heparinized blood samples were immediately cooled on ice and then centrifuged at 3,000 rpm (4 ℃) for 10 min. Following administration of the SR formulation, blood samples were collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, and 48 h. For evaluation of lacosamide levels following oral administration of Vimpat ® to mini-pigs, 1 mL blood samples were collected from the jugular vein immediately before administration, and at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 12.5, 13, 13.5, 14, 15, 18, 24, 30, 36, and 48 h after administration. For evaluation of lacosamide levels following oral administration of Vimpat ® to the dogs, 1 mL blood samples were collected from the jugular vein immediately before administration, and at 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 12.5, 13, 13.5, 14, 15, 18, 24, 30, 36, and 48 h after administration. The SR tablet (100 mg lacosamide) was administered once daily, whereas Vimpat ® (50 mg lacosamide) was administered twice daily. Each dog or pig received either a SR tablet (formulation 1) or Vimpat ® tablets, with a washout period of 2 weeks before switching to the other formulation. ![]() The study was carried out using a randomized crossover design, with the animals divided into two groups of three. They had free access to food and water, except for immediately prior to each experiment, when they were fasted overnight with free access to water. All animals were kept in a temperature-controlled environment (22 ± 2 ℃) with a 12 h light-dark cycle. All animals were treated in accordance with the Guide for the Care and Use of Laboratory Animals, from the National Institutes of Health (USA). Six male beagle dogs (12 ± 7 kg) and six mini-pigs (20 ± 5 kg) were used in the pharmacokinetic studies. 11 12 Large fluctuations in plasma lacosamide concentrations can also produce these unwanted side effects, which limit the usefulness of oral lacosamide in some patients. These include visual disturbances and prolongation of the P-R electrocardiogram interval between the start of atrial systole and the start of ventricular systole, leading to AV (atrioventricular) node blockage. 8 Moreover, the rapid and complete absorption of lacosamide after oral administration poses a problem as it can lead to a high C max followed by a high steady-state concentration, resulting in a greater frequency of adverse pharmacological events. 1 5 However, This is not optimal because patient compliance decreases as the dosing frequency of a drug increases. Lacosamide has an elimination half-life of about 13 h, making it an ideal candidate for twice daily dosing with an immediate release formulation. T max usually occurs between 1 and 4 h after administration and food does not affect the rate or extent of absorption. 6 7 Lacosamide has an aqueous solubility of about 27 g/L, and is rapidly and completely absorbed by the body following firstorder kinetics. After single-dose oral or intravenous administration, the plasma concentration of lacosamide increases in a dose-dependent manner with oral doses up to 800 mg and intravenous doses up to 300 mg. ![]() The pharmacokinetic profile of lacosamide exhibits low intra- and inter-patient variability.
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