Gabix Mechanism of Action

Pharmacology: Mechanism of Action: Gabapentin has proven affinity for special site in brain tissues eg, neocortex and hippocampus. Though exact mechanism of its central nervous system (CNS) depressant and anticonvulsant activity is not fully understood, it is thought to be activated through peptide binding sites (receptor). It also has analgesic activity.
Pharmacokinetics: Absorption: Gabapentin is absorbed from the gastrointestinal tract (GIT) by means of saturable mechanism. Gabapentin bioavailability is not dose proportional ie, as dose is increased, bioavailability is decreased. Absolute bioavailability of 300-mg oral dose is approximately 60%. At doses of 300 and 400 mg, gabapentin bioavailability was unchanged following multiple dose administration. Food has no effect on the rate and extent of absorption.
Distribution: Gabapentin circulates largely unbound (<3%) to plasma proteins. It is distributed into breast milk and has a volume of distribution equal to 57.7 L.
Metabolism and Elimination: Gabapentin is not appreciably metabolized and is eliminated from the systemic circulation by renal excretion as unchanged drug. Elimination t_½ ranges from 5-7 hrs and is unaltered by dose or following multiple dosing. Gabapentin elimination rate constant, plasma and renal clearance are directly proportional to creatinine clearance (CrCl).
Special Populations: Renal Insufficiency: The mean gabapentin t_½ ranged from about 6.5 hrs (patients with CrCl >60 mL/min) to 52 hrs (CrCl <30 mL/min) and gabapentin renal clearance ranged from 90 mL/min (CrCl >60 mL/min) to about 10 mL/min (CrCl <30 mL/min). Gabapentin dosage should be adjusted in patients with compromised renal function.
Patients on Hemodialysis: In anuric patients, the elimination t_½ of gabapentin on a nondialysis day was about 132 hrs; during dialysis the apparent t_½ was reduced to 3.8 hrs. Thus, hemodialysis has a significant effect on gabapentin elimination in anuric patients. Gabapentin dosage should be adjusted in patients undergoing hemodialysis.
Elderly: The apparent oral clearance (CL/F) of gabapentin decreased as age increased, from about 225 mL/min in those <30 years to about 125 mL/min in those >70 years. Reduction of gabapentin dose may be required in patients who have age-related compromised renal function.
Drug-Drug Interactions: Naproxen: Co-administration of naproxen sodium (250 mg) with gabapentin (125 mg) appears to increase the amount of gabapentin absorbed by 12-15%. These doses are lower than the therapeutic doses for both drugs. The magnitude of interaction within the recommended dose is not known.
Hydrocodone: Co-administration of gabapentin decreases hydrocodone C_max and area under the curve (AUC) values in a dose-dependent manner relative to administration of hydrocodone alone. Hydrocodone increases gabapentin AUC values by 14%.
Morphine: When morphine 60 mg is administered 2 hrs prior to gabapentin 600 mg, the mean gabapentin AUC increased by 44% compared to gabapentin administered without morphine.