Where is neurontin metabolized

Gabapentin increases non-synaptic GABA responses from neuronal tissues in vitro. In vitro, gabapentin reduces the release of several mono-amine neurotransmitters. Gabapentin prevents pain responses in several animal models of hyperalgesia and prevents neuronal death in vitro and in vivo with models of the neurodegenerative disease amyotrophic lateral sclerosis ALS. Increased as needed and tolerated to 1, mg daily, given in three divided doses.

Usual dosage is to mg P. Postherpetic neuralgia. Adults: mg P. Adjust as needed to a maximum daily dose of 1, mg divided into three doses. For patients age 12 and older with compromised renal function and patients receiving hemodialysis, use the dosage guide at the top of the next column.

Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance as indicated below and a supplemental posthemodialysis dose of to mg administered after each 4 hours of hemodialysis. Pharmacodynamics Anticonvulsant action: Mechanism of action is unknown. Gabapentin is known to be effective in the treatment of neuropathic pain [1]. The analgesic mechanism of action of gabapentin has yet to be fully elucidated.

Recent work using animal and human models demonstrates one possible mechanism is through the selective inhibition of the alpha 2 delta subunit of voltage-gated calcium channels [2]. Its relatively benign side-effect profile has undoubtedly contributed to its widespread use; several studies have documented only mild clinical effects following significant gabapentin overdose [3,4]. Gabapentin is not significantly metabolized and is excreted solely by the kidney.

Thus, plasma levels will rise as renal clearance falls. For this reason, dose adjustment is recommended in patients with renal failure [5]. Failure to account for reduced gabapentin elimination in patients with renal impairment can lead to serious toxicity. Several investigators have reported neurological sequelae following administration of the drug to patients with renal failure [6—8].

These have included subtle changes in mental status, drowsiness, and even coma. Fortunately, gabapentin is removed by renal replacement therapy [9] , and if prompt treatment is instituted, the neurological toxicity is completely reversible. Our case report highlights the need for diligent prescribing. Accumulation of the drug may have contributed to the fall and drowsiness that led to her admission.

As her renal function deteriorated, appropriate changes to her drug prescription chart were made to prevent further drug toxicity—but her gabapentin dose was not adjusted. Thus, iatrogenic toxicity continued for several days. The assay for serum gabapentin level is not readily available, but the history, examination findings, and the patient's rapid clinical improvement with CVVH all point toward gabapentin toxicity. Gabapentin has a nonlinear relationship between therapeutic and toxic levels and exhibits a wide interpatient variability [10] , making the analysis of plasma levels of limited use other than to confirm the presence of gabapentin.

It is increasingly recognized that inappropriate use of medication in the elderly—in our patient the off-label prescription of gabapentin for non-neuropathic pain—leads to adverse drug events [12].

Education for all doctors about the importance of gabapentin dosage adjustment in renal failure could prevent many similar events from occurring in the future. Gabapentin for acute and chronic pain. Google Scholar. Sills GJ. The mechanisms of action of gabapentin and pregabalin. Curr Opin Pharmacol ; 6 1 : — A case of sustained massive gabapentin overdose without serious side effects.

Ther Drug Monit ; 21 6 : — 7. Characterization of gabapentin overdose using a poison center case series. J Toxicol Clin Toxicol ; 41 1 : 11 — 5. Gabapentin-induced coma in a patient with renal failure. Hemodial Int ; 10 2 : — 9. Gabapentin neurotoxicity in a chronic haemodialysis patient. Nephrol Dial Transplant ; 16 10 : — 3.

The drug is excreted unchanged in urine; plasma clearance is linearly related to creatinine clearance; and dosage is readily adjusted based on renal function. The elimination half-life is approximately 5 to 9 hours. Consequently, three divided doses are usually required per day, but steady state is rapidly achieved.