However, this activation is unlikely to be the dominant mechanism of gabapentins therapeutic effects.Despite the fact that gabapentin is a structural GABA analogue, and in spite of its name, it does not bind to the GABA receptors, does not convert into GABA or another GABA receptor agonist in vivo, and does not modulate GABA transport or metabolism. Pharmacokinetics
Gabapentin is absorbed from the intestines by an active transport process mediated via an amino acid transporter, presumably, LAT2. As a result, the pharmacokinetics of gabapentin is dose-dependent, with diminished bioavailability and delayed peak levels at higher doses.The oral bioavailability of gabapentin is approximately 80% at 100 mg administered three times daily once every 8 hours, but decreases to 60% at 300 mg, 47% at 400 mg, 34% at 800 mg, 33% at 1,200 mg, and 27% at 1,600 mg, all with the same dosing schedule. Drugs that increase the transit time of gabapentin in the small intestine can increase its oral bioavailability; when gabapentin was co-administered with oral morphine, the oral bioavailability of a 600 mg dose of gabapentin increased by 50%.Gabapentin at a low dose of 100 mg has a Tmax (time to peak levels) of approximately 1.7 hours, while the Tmax increases to 3 to 4 hours at higher doses. Food does not significantly affect the Tmax of gabapentin and increases the Cmax and area-under-curve levels of gabapentin by approximately 10%.Gabapentin can cross the blood–brain barrier and enter the central nervous system. Gabapentin concentration in cerebrospinal fluid is approximately 9–14% of its blood plasma concentration.
This is a general recommendation applicable to all neuropathic pain syndromes except for trigeminal neuralgia.In regard to the specific diagnoses, the best evidence exists for gabapentin treatment of postherpetic neuralgia and diabetic neuropathy. Gabapentin is approved for the former indication in the US. In addition to these two neuropathies, European Federation of Neurological Societies guideline notes gabapentin effectiveness for central pain. A combination of gabapentin with an opioid or nortriptyline may work better than either drug alone.Overall, gabapentin shows moderate effectiveness for neuropathic pain. Only a minority of patients obtain meaningful relief. Out of 10 persons treated with gabapentin, three to four benefit substantially as compared to one to two persons treated with placebo.Evidence finds little or no benefit and significant risk in those with chronic low back pain or sciatica. Gabapentin is not effective in HIV-associated sensory neuropathy and neuropathic pain due to cancer. Anxiety
There is a small amount research on the use of gabapentin for the treatment of anxiety disorders. In a controlled trial of breast cancer survivors with anxiety, and in a trial for social phobia, gabapentin significantly reduced anxiety levels. For panic disorder, gabapentin is ineffective. Conversely, some psychiatric textbooks see "a possible role for gabapentin in anxiety disorders, particularly social phobia and panic disorder" based on "case reports and double-blind studies" or state that controlled studies have not shown gabapentin to be very effective for psychiatric indications; "however, clinically it is effective". Sleep
Gabapentin is effective in treating sleep disorders such as insomnia and restless legs syndrome.