Preliminary studies suggest that gabapentin is associated with α 2 -δ-subunit of voltage-dependent calcium channels and inhibits the flow of calcium ions, which plays an important role in the onset of neuropathic pain.Other mechanisms involved in the action of gabapentin for neuropathic pain are: reduction of glutamate-dependent neuronal death, increasing GABA synthesis, inhibition of monoamine neurotransmitter release group. Gabapentin buy testosterone enanthate at clinically relevant concentrations, does not bind to other receptors or neurotransmitters common drugs, including GAMKd receptors, GABA B, benzodiazepine, glutamate, glycine, or N-methyl-d-aspartate. Unlike phenytoin and carbamazepine, gabapentin does not interact with sodium channels in vitro. Gabapentin partially attenuated effects receptor agonist glutamate N-methyl-D-aspartate in some tests in vitro, but only at a concentration of more than 100 micromoles, which is not achieved in vivo. Gabapentin slightly reduces the release of monoamine neurotransmitters in vitro. Use of gabapentin in the rat resulted in an increase in GABA metabolism of certain areas of the brain; This effect was similar to that of sodium valproate, although observed in other brain regions. The significance of these effects of gabapentin to its anticonvulsant activity is not established.Animals gabapentin easily penetrate brain tissue and prevents seizures induced by maximal electroshock, chemical agents, including inhibitors of GABA synthesis, as well as due to genetic factors.
The bioavailability of gabapentin is not proportional to dose; Thus, with increasing dose is reduced. After oral administration, maximum concentration (C max ) of gabapentin in plasma achieved in 2-3 hours. The absolute bioavailability of gabapentin capsules is approximately 60%. Food, including a high content of fat, has no effect on pharmacokinetics. Excretion of gabapentin plasma is best described by a linear model. The half-life (T 1/2 ) in plasma is independent of dose and averages 5-7 hours Pharmacokinetics does not change with repeated use.; equilibrium plasma concentration can be predicted on the basis of the results of a single dose. Gabapentin is almost bound to plasma proteins (<3%) and has a volume of distribution of 57.7 liters. Displayed only kidneys unchanged, metabolic features not found in humans. The drug does not induce liver oxidative enzymes mixed function involved in the metabolism of drugs. Clearance from plasma gabapentin reduced in the elderly and patients with impaired renal function. The constant rate of excretion, clearance from the plasma and renal clearance are directly proportional to creatinine clearance. Gabapentin is removed from plasma by hemodialysis. In patients with impaired renal function and patients receiving hemodialysis, dose adjustment is recommended (see. Dosing and Administration, Table 1). It is found that the plasma concentration of gabapentin in children between the ages of 4 and 12 are generally similar to those in adults.
Treatment of neuropathic pain in buy testosterone enanthate adults aged 18 years and older. Efficacy and safety in patients below the age of 18 years have not been established.
Monotherapy with partial seizures with secondary generalization and without adults and children over the age of 12 years. The efficacy and safety of monotherapy in children under the age of 12 years have not been established.
As an additional tool in the treatment of partial seizures with secondary generalization and without adults and children aged 3 years and older. Safety and efficacy of gabapentin adjunctive therapy in children aged less than 3 years have not been established.
: Hypersensitivity to gabapentin or auxiliary ingredients. These dosage forms are not intended for use in children under the age of 3 years.
Renal failure (see. “Dosage and administration”).
Application of pregnancy and during breast-feeding
There are no data on the use of the drug in pregnant women, therefore, gabapentin should be used during pregnancy only if the expected benefit to the mother justifies the potential risk to the fetus.
Gabapentin is excreted in breast milk, its effect on breastfed the child is not known, therefore during lactation Neurontin should be used only if the benefit to the mother clearly outweighs the risk to the baby.
Dosage and administration
Neurontin is prescribed orally with or without food, or with food. If you need to reduce the dose, stop the drug or replace it with an alternative means, it should be done gradually over a minimum of one week.Neuropathic pain in adults initial dose is 900 mg / day in three divided doses equal doses; if necessary, depending on the effect of gradually increasing the dose until a maximum – 3600 mg / day. Treatment may start with a dose of 900 mg / day (300 mg three times a day) or within the first 3 days the dose may be increased gradually to 900 mg a day according to the following scheme: Day 1: 300 mg 1 time day2nd day: 300 mg 2 times a day 3rd day: 300 mg 3 times daily partial seizures Adults and children over the age of 12 years: The effective dose – from 900 to 3600 mg / day. Therapy can be buy testosterone enanthate started with a dose of 300 mg three times a day on the first day and increased gradually to 900 mg according to the scheme described above (see., “Neuropathic pain in adults” section). Subsequently, the dose may be increased to a maximum of 3600 mg / day (divided into three equal doses). It was well tolerated in doses up to 4800 mg / day. The maximum interval between doses at three receiving the drug should not exceed 12 hours in order to avoid the resumption of seizures. Children aged 3-12 years: The initial dose of the drug varies from 10 to 15 mg / kg / day, which is equal doses administered 3 times a day and increase to effectively for about 3 days. The effective dose of gabapentin in children aged 5 years and older is 25-35 mg / kg / day in 3 equal doses reception. The effective dose of gabapentin in children aged 3 to 5 years is 40 mg / kg / day in 3 equal doses reception. It was well tolerated in doses up to 50 mg / kg / day for prolonged use. The maximum interval between doses doses should not exceed 12 hours in a resumption prevent seizures. There is no need to control the concentration of gabapentin in plasma.