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PubMed2006

The use of gabapentin for post-operative and post-traumatic pain in thoracic surgery patients.

OBJECTIVE: The pain following thoracic surgery and trauma is often refractory to conventional analgesic strategies. However, it shares key characteristics with neuropathic pain which gabapentin, an anticonvulsant, has been proven to effectively treat. To our knowledge, this is the first prospective study assessing the use of gabapentin in cardiothoracic surgery patients. METHODS: Gabapentin was prescribed to 60 consecutive out-patients with refractory pain persisting at four weeks or more after thoracic surgery or trauma. Follow-up of 45 patients (75%) was performed for a median of 21 months (range: 12-28), and clinical data collected prospectively. The mean age of these patients was 51.6 years (range 22-83). Of these 45 patients, 22 had received video-assisted thoracic surgery (VATS), 8 had received thoracotomy, 3 had received median sternotomy, and 12 were treated for blunt chest trauma. RESULTS: The mean duration of pre-treatment refractory pain was 5.76 months (range 1-62). The mean duration of gabapentin use was 21.9 weeks (range 1-68). No deaths or major complications were encountered. Minor side effects-mostly somnolence and dizziness-occurred in 18 patients (40.0%), causing 3 patients (6.7%) to discontinue gabapentin. Overall, 33 patients (73.3%) noted reduction of pain. Chest wall paresthesia distinguishable from wound pain was relieved in 24 (75.0%) of 32 affected patients. Severe initial pain was significantly correlated with pain relief using gabapentin (p=0.009). No other demographical or clinical variable correlated with benefit or side effects. Satisfaction with gabapentin use was expressed by 40 patients (88.9%). Side effects were not a source of dissatisfaction in any patient. CONCLUSIONS: Gabapentin appears safe and well tolerated when used for persistent post-operative and post-traumatic pain in thoracic surgery patients, although minor side effects do occur. Gabapentin may relieve refractory chest wall pain in some of these patients, particularly those with more severe pain. Further studies are warranted to define the role of gabapentin in cardiothoracic surgical practice.

Adult↗
PubMed2004

Gabapentin for the prevention of postoperative pain after vaginal hysterectomy.

Gabapentin alleviates and/or prevents acute nociceptive and inflammatory pain both in animals and volunteers, especially when given before trauma. Gabapentin might also reduce postoperative pain. To test the hypothesis that gabapentin reduces the postoperative need for additional pain treatment (postoperative opioid sparing effect of gabapentin in humans), we gave 1200 mg of gabapentin or 15 mg of oxazepam (active placebo) 2.5 h prior to induction of anaesthesia to patients undergoing elective vaginal hysterectomy in an active placebo-controlled, double blind, randomised study. Gabapentin reduced the need for additional postoperative pain treatment (PCA boluses of 50 microg of fentanyl) by 40% during the first 20 postoperative hours. During the first 2 postoperative hours pain scores at rest and worst pain score (VAS 0-100 mm) were significantly higher in the active placebo group compared to the gabapentin-treated patients. Additionally, pretreatment with gabapentin reduced the degree of postoperative nausea and incidence of vomiting/retching possibly either due to the diminished need for postoperative pain treatment with opioids or because of an anti-emetic effect of gabapentin itself. No preoperative differences between the two groups were encountered with respect to the side effects of the premedication. However, 15 mg oxazepam was more effective in relieving preoperative anxiety than 1200 mg gabapentin.

Acetates↗
PubMed2006

Gabapentin's acute effect on mood profile -- a controlled study on patients with alcohol withdrawal.

RATIONALE: Delayed beneficial effects of gabapentin on mood were frequently reported in various patient populations. This is the first controlled study which addressed acute effects of gabapentin on mood. METHODS: Analysis of the German version of Profile of Mood States (POMS) throughout a randomised placebo-controlled, double-blinded study of gabapentin on acute alcohol withdrawal [Bonnet, U., Banger, M., Leweke, F.M., Specka, M., Müller, B.W., Hashemi, T., Nyhuis, P.W., Kutscher, S., Burtscheidt, W., Gastpar, M. 2003. Treatment of acute alcohol withdrawal with gabapentin -- results from a controlled two-center trial. J Clin Psychopharmacol 23, 514-519]. In addition, subjective severity of alcohol withdrawal was determined by the Essen Self-Assessment of Alcohol Withdrawal Scale (ESA) to control effects of concurrent withdrawal on POMS. Ratings were performed at intake (baseline), day 1 (study medication 400 mg q.i.d.), day 2 (study medication 400 mg q.i.d.) and day 7 (no study medication). RESULTS: Analyses could be performed on 46 out of 59 randomised subjects. Within the first two days of the study, a significant stronger increase in the POMS-vigour subscore occurred in the gabapentin group. A subgroup analysis suggests that gabapentin's effect on vigour largely results from a stronger improvement of vigour in a small group of 11 patients with co-morbid mild depression (according to ICD-10: dysthymia or depressive adjustment disorder). There were no significant differences between the treatment groups regarding the other POMS-subscores (dejection, fatigue, anger) ruling out an overall fast effect on mood. Moreover, ESA-measures were not significantly altered indicating a missing effect of 400 mg gabapentin q.i.d. on acute alcohol withdrawal itself. After tapering off study medication, no more significant differences between gabapentin and placebo group were observed on vigour, strongly suggesting that the initial effect results from a pharmacological gabapentin action. CONCLUSION: Gabapentin selectively accelerated the improvement of the vigour-subscore of patients with acute alcohol withdrawal within 48 h. This effect was independent from the subjective severity of withdrawal and especially marked in patients with co-morbid mild depression.

Adult↗
PubMed2000

Allosteric modulation of [(3)H]gabapentin binding by ruthenium red.

Gabapentin is an anticonvulsant with an unknown mechanism of action. However, it has been proposed that gabapentin acts by binding to voltage-gated calcium channels. To further characterize the interaction of gabapentin with its endogenous binding site in cerebral cortex, we tested for competitive and allosteric interactions between [(3)H]gabapentin and a variety of calcium channel binding ligands. Most ligands for voltage- or ligand-gated calcium channels (verapamil, the omega-conotoxins MVIIC and GVIA, ryanodine, caffeine, capsaicin, MK-801) had no significant effect on [(3)H]gabapentin binding. However, ruthenium red, a relatively nonselective calcium channel ligand, was found to robustly modulate [(3)H]gabapentin binding. Ruthenium red slowed the association and dissociation kinetics of [(3)H]gabapentin while increasing the number of detectable binding sites. Spermine and MgCl(2), which also bind to calcium channels and modulate [(3)H]gabapentin binding, were found to act in a similar manner. These findings support the contention that the principal endogenous binding site for gabapentin is a calcium channel; they characterize the nature of the allosteric interaction of spermine, MgCl(2) and ruthenium red with this binding site; and they suggest possible mechanisms by which gabapentin may modulate calcium channel function and ultimately produce therapeutic actions.

Acetates↗
PubMed1996

Gabapentin in generalized seizures.

The efficacy of gabapentin (Neurontin), in generalized seizures was evaluated in this 14 week, double-blind, placebo-controlled, parallel-group, add-on, multicenter study. A total of 129 patients with refractory generalized seizures were randomized to receive either placebo or 1200 mg/day gabapentin as add-on therapy. Patients received their standard regimens of antiepileptic drugs (AEDs) during a 12 week baseline period, and gabapentin or placebo was added-on in the subsequent 14 week evaluation period. Results of both an intent-to-treat (ITT) and evaluable-patient analyses showed that gabapentin provided greater reduction in the frequency of generalized tonic-clonic seizures than did placebo; however, the differences between treatments were not statistically significant. Gabapentin did not affect the frequency of absence or myoclonic seizures. Adverse events were reported by 67% of gabapentin-treated patients and by 56% of placebo-treated patients. The most frequently occurring adverse events among patients receiving gabapentin were somnolence, fatigue, and dizziness. Gabapentin is well tolerated by patients with generalized seizures. The results of this study show a trend toward an effect of gabapentin in reducing the frequency of generalized tonic-clonic seizures and suggest that further exploration of high dose gabapentin in generalized epilepsy is warranted.

Acetates↗
PubMed2005

Role of descending noradrenergic system and spinal alpha2-adrenergic receptors in the effects of gabapentin on thermal and mechanical nociception after partial nerve injury in the mouse.

1. To gain further insight into the mechanisms underlying the antihyperalgesic and antiallodynic actions of gabapentin, a chronic pain model was prepared by partially ligating the sciatic nerve in mice. The mice then received systemic or local injections of gabapentin combined with either central noradrenaline (NA) depletion by 6-hydroxydopamine (6-OHDA) or alpha-adrenergic receptor blockade. 2. Intraperitoneally (i.p.) administered gabapentin produced antihyperalgesic and antiallodynic effects that were manifested by elevation of the withdrawal threshold to a thermal (plantar test) or mechanical (von Frey test) stimulus, respectively. 3. Similar effects were obtained in both the plantar and von Frey tests when gabapentin was injected intracerebroventricularly (i.c.v.) or intrathecally (i.t.), suggesting that it acts at both supraspinal and spinal loci. This novel supraspinal analgesic action of gabapentin was only obtained in ligated neuropathic mice, and gabapentin (i.p. and i.c.v.) did not affect acute thermal and mechanical nociception. 4. In mice in which central NA levels were depleted by 6-OHDA, the antihyperalgesic and antiallodynic effects of i.p. and i.c.v. gabapentin were strongly suppressed. 5. The antihyperalgesic and antiallodynic effects of systemic gabapentin were reduced by both systemic and i.t. administration of yohimbine, an alpha2-adrenergic receptor antagonist. By contrast, prazosin (i.p. or i.t.), an alpha1-adrenergic receptor antagonist, did not alter the effects of gabapentin. 6. It was concluded that the antihyperalgesic and antiallodynic effects of gabapentin are mediated substantially by the descending noradrenergic system, resulting in the activation of spinal alpha2-adrenergic receptors.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1997

Effectiveness of gabapentin in controlling spasticity: a quantitative study.

The purpose of this investigation was to study the effectiveness of gabapentin in controlling spasticity in persons with spinal cord injury (SCI) using a surface EMG-based quantitative assessment technique called the brain motor control assessment (BMCA). Six men from a Veterans Affairs Medical Center with spasticity due to traumatic SCI were studied as part of a multi-center, placebo-controlled, cross-over, clinical trial of gabapentin. Spasticity was evaluated using multi-channel surface EMG recordings of muscles in the lower extremities, abdomen and low back before and during treatment with oral gabapentin or placebo. Gabapentin or placebo was given orally in doses 400 mg three times daily for 48 h. Following a 10 day wash-out period subjects were crossed-over to receive the medication not received the first time. This was followed by an elective open-label extension. Group results during the controlled trial did not reach statistical significance at the dosage used. One subject demonstrated a dramatic improvement in spasticity that was apparent both clinically and with the BMCA. Other subjects demonstrated modest improvements which were seen in the BMCA but not recognized clinically. During the open label extension, the four subjects who participated experienced important clinical improvements with higher doses (to 3600 mg/day). These improvements were often in components of spasticity in which the BMCA had detected subclinical changes during the cross-over trial. A seventh subject was studied using the BMCA at doses of 1200 mg T.I.D. gabapentin, off gabapentin and 800 mg T.I.D. gabapentin and demonstrated quantitatively a dose-related effect with higher doses of gabapentin which matched clinical observations. Gabapentin at doses of 400 mg T.I.D. may be effective in controlling some features of spasticity in persons with SCI. Higher doses provide greater control of spasticity, and controlled studies using higher doses are needed to evaluate gabapentin's efficacy.

Acetates↗
PubMed1995

Transport of gabapentin, a gamma-amino acid drug, by system l alpha-amino acid transporters: a comparative study in astrocytes, synaptosomes, and CHO cells.

The system L transporter is generally considered to be one of the major Na(+)-independent carriers for large neutral alpha-amino acids in mammalian cells. However, we found that cultured astrocytes from rat brain cortex accumulate gabapentin, a gamma-amino acid, predominately by this alpha-amino acid transport system. Uptake of gabapentin by system L transporter was also examined in synaptosomes and Chinese hamster ovary (CHO) cells. The inhibition pattern displayed by various amino acids on gabapentin uptake in astrocytes and synaptosomes corresponds closely to that observed for the system L transport activity in CHO cells. Gabapentin and leucine have Km values that equal their Ki values for inhibition of each other, suggesting that leucine and gabapentin compete for the same system L transporter. By contrast, gabapentin exhibited no effect on uptake of GABA, glutamate, and arginine, indicating that these latter three types of brain transporters do not serve for uptake of gabapentin. A comparison of computer modeling analysis of gabapentin and L-leucine structures shows that although the former is a gamma-amino acid, it can assume a conformation that can resemble the L-form of a large neutral alpha-amino acid such as L-leucine. The steady-state kinetic study in astrocytes and CHO cells indicates that the intracellular concentrations of gabapentin are about two to four times higher than that of leucine. The uptake levels of these two substrates are inversely related to their relative exodus rates. The concentrating ability by system L observed in astrocytes is consistent with the substantially high accumulation gradient of gabapentin in the brain tissue as determined by microdialysis.

Acetates↗
PubMed2004

Chronic oral gabapentin reduces elements of central sensitization in human experimental hyperalgesia.

BACKGROUND: In chronic pain, increased activity from intact or damaged peripheral nerve endings results in an enhanced response in central pain transmission systems, a mechanism known as central sensitization. Central sensitization can also be invoked in human experimental models. Therefore, these models may be useful to characterize novel analgesics in humans. The anticonvulsant gabapentin has demonstrated efficacy in patients with neuropathic pain, but its mode of action remains unclear. This study examined the effects of gabapentin on signs of central sensitization (brush and pinprick hyperalgesia) in a human model of capsaicin-evoked pain, using a gabapentin dosing regimen similar to that used in the clinic. The aims were to determine whether gabapentin, dosed in a manner similar to that used in the clinic, affected the various components of central sensitization and to assess the utility of this model for characterizing novel analgesics. METHODS: Intradermal capsaicin (100 microg/20 microl) was administered in the volar forearm of 41 male human volunteers to induce pain and clinical signs of central sensitization. Gabapentin (titrated to 2,400 mg daily) or placebo was given orally for 15 days in a randomized, double-blind, parallel-group design. The capsaicin test was conducted at baseline and after gabapentin or placebo. Endpoints were the size of areas of brush-evoked allodynia (with cotton gauze) and pinprick hyperalgesia (with von Frey filament), and the intensity of ongoing brush- and pinprick-evoked pain. RESULTS: Gabapentin significantly reduced the area of brush allodynia compared with placebo (P </= 0.05) and insignificantly attenuated the area of pinprick hyperalgesia. Gabapentin had no significant effect on spontaneous and evoked pain intensity. CONCLUSION: Oral gabapentin, administered to healthy volunteers in a regimen similar to that used in treating chronic neuropathic pain, reduces measures of central sensitization evoked by intradermal capsaicin. This suggests that the pain-relieving effect in chronic neuropathic pain condition is linked to the effect of gabapentin on central sensitization. The ability of the capsaicin model to detect the efficacy of this standard treatment of neuropathic pain suggests that it may have a predictive value for detection of efficacy in human subjects.

Adult↗
PubMed2005

Gabapentin withdrawal syndrome in the presence of a taper.

OBJECTIVE: To report a case report of a geriatric patient with a 5-year history of gabapentin use for enhanced bipolar control, who was tapered off of gabapentin over 1 week. The patient displayed unique withdrawal symptoms after the taper of gabapentin. METHODS: The patient is an 81-year-old white female with a life-long history of schizoaffective disorder with bipolar type I tendencies who had been prescribed gabapentin for 5 years. RESULTS: The patient displayed moderate upper respiratory tract infection symptoms and somatic complaints 1 day after termination of gabapentin. These symptoms gradually worsened until 10 days after, at which time she acutely developed severe mental status changes, severe somatic chest pain, and hypertension. Physical examination, electrolytes, electrocardiogram, computerized tomography, magnetic resonance imaging, and magnetic resonance angiography were all normal. Upon reintroduction of gabapentin, the patient returned to baseline within 1-2 days. CONCLUSIONS: Gabapentin is widely utilized currently for the chronic treatment of recalcitrant migraines, bipolar illness, pain, and epilepsy. It has a wide therapeutic index with few side effects and drug interactions, is not hepatically metabolized, and is excreted by the kidneys. Past reports have suggested that some withdrawal symptoms can present after 1-2 days upon abrupt discontinuation of gabapentin after chronic use within young to middle-aged patients. These symptoms mimic that of alcohol and benzodiazepine withdrawal purportedly due to a similar mechanism of action. Unique to this case is that this geriatric patient developed debilitating withdrawal symptoms after a gradual, week-long taper of gabapentin along with flu-like symptoms. It is proposed herein that a gabapentin taper should follow a course similar to that of a benzodiazepine taper -- slowly and over a period of weeks to months.

Aged↗
PubMed2005

Evidence that gabapentin reduces neuropathic pain by inhibiting the spinal release of glutamate.

Gabapentin is an anticonvulsant that successfully treats many neuropathic pain syndromes, although the mechanism of its antihyperalgesic action remains elusive. This study aims to help delineate gabapentin's antihyperalgesic mechanisms. We assessed the effectiveness of gabapentin at decreasing mechanical and cold hypersensitivity induced in a rat model of neuropathic pain. Thus, we compared the effectiveness of pre- or post-treatment with systemic or intrathecal (i.t.) gabapentin at reducing the development and maintenance of the neuropathic pain symptoms. Gabapentin successfully decreased mechanical and cold hypersensitivity, both as a pretreatment and post-treatment. Furthermore, both i.t. and systemic administration of gabapentin were effective in reducing the behavioral hypersensitivity; however, the i.t. administration was superior to the systemic. We also examined gabapentin's effects at inhibiting hindpaw formalin-induced release of excitatory amino acids (EAAs) in the spinal cord dorsal horn (SCDH) both in naïve rats and in rats with neuropathic pain. We present the first evidence that gabapentin reduces the formalin-induced release of both glutamate and aspartate in SCDH. Furthermore, i.t. gabapentin reduces the enhanced noxious stimulus-induced spinal release of glutamate seen in neuropathic rats. These data suggest that gabapentin reduces neuropathic pain symptoms by inhibiting the release of glutamate in the SCDH.

Amines↗
PubMed2007

Premedication with gabapentin: the effect on tourniquet pain and quality of intravenous regional anesthesia.

BACKGROUND: Gabapentin, an oral non-opioid analgesic, has been used to decrease pain after a variety of surgical procedures. We hypothesized that premedication with gabapentin would minimize tourniquet-related pain in patients receiving IV regional anesthesia (IVRA). METHODS: Patients undergoing elective hand surgery with IVRA were randomly assigned to one of two study groups using a double-blind study design. The control group (n = 20) received placebo capsules 1 h before the surgery, and the gabapentin group (n = 20) received gabapentin 1.2 g p.o. before the operation. IVRA was achieved in all patients with lidocaine, 3 mg/kg, diluted with saline to a total volume of 40 mL. Fentanyl, 0.5 microg/kg IV, was administered as a rescue analgesic during surgery. Sensory and motor block onset and recovery times, tourniquet pain, and quality of anesthesia were assessed at specific time intervals during the perioperative period. Visual analog scale pain scores (0-10) were recorded during the 24 h follow-up period, and patients received diclofenac, 75 mg IM, if their pain score was >4. RESULTS: The onset of the sensory and motor block did not differ between the two study groups. However, tourniquet pain scores at 30, 40, 50, and 60 min after cuff inflation were lower in the gabapentin group (P < 0.05). The time to intraoperative analgesic rescue was prolonged in the gabapentin group (35 +/- 10 min vs 21 +/- 13 min, P < 0.05), and less supplemental fentanyl was required (35 +/- 47 microg vs 83 +/- 73 microg, P < 0.05). The quality of anesthesia, as independently assessed by the anesthesiologist and the surgeon, was significantly better in the gabapentin (versus control) group. In the gabapentin group, the time to requesting a rescue analgesic after surgery was prolonged (135 +/- 25 min vs 85 +/- 19 min, P < 0.05), and postoperative pain scores at 60 min (3.8 +/- 0.9 vs 2.2 +/- 0.5) and 120 min (3.2 +/- 1.4 vs 1.8 +/- 0.8), as well as diclofenac consumption (30 +/- 38 mg vs 60 +/- 63 mg), were reduced after surgery. CONCLUSIONS: Premedication with oral gabapentin (1.2 g) decreased tourniquet-related pain and improved the quality of anesthesia during hand surgery under IVRA. Gabapentin also reduced pain scores in the early postoperative period.

Adult↗
PubMed1999

Structural requirement of the calcium-channel subunit alpha2delta for gabapentin binding.

Gabapentin [Neurontin, 1-(aminomethyl)cyclohexaneacetic acid] is a novel anticonvulsant drug with a high binding affinity for the Ca(2+)-channel subunit alpha(2)delta. In this study, the gabapentin-binding properties of wild-type and mutated porcine brain alpha(2)delta proteins were investigated. Removal of the disulphide bonds between the alpha(2) and the delta subunits did not result in a significant loss of gabapentin binding, suggesting that the disulphide linkage between the two subunits is not required for binding. Singly expressed alpha(2) protein remained membrane associated. However, alpha(2) alone was unable to bind gabapentin, unless the cells were concurrently transfected with the expression vector for delta, suggesting that both alpha(2) and delta are required for gabapentin binding. Using internal deletion mutagenesis, we mapped two regions [amino acid residues 339-365 (DeltaF) and 875-905 (DeltaJ)] within the alpha(2) subunit that are not required for gabapentin binding. Further, deletion of three other individual regions [amino acid residues 206-222 (DeltaD), 516-537 (DeltaH) and 583-603 (DeltaI)] within the alpha(2) subunit disrupted gabapentin binding, suggesting the structural importance of these regions. Using alanine to replace four to six amino acid residues in each of these regions abolished gabapentin binding. These results demonstrate that region D, between the N-terminal end and the first putative transmembrane domain of alpha(2), and regions H and I, between the putative splicing acceptor sites (Gln(511) and Ser(601)), may play important roles in maintaining the structural integrity for gabapentin binding. Further single amino acid replacement mutagenesis within these regions identified Arg(217) as critical for gabapentin binding.

Acetates↗
PubMed1998

Reduction of 3,4-diaminopyridine-induced biogenic amine synthesis and release in rat brain by gabapentin.

The anticonvulsant drug gabapentin has been shown recently to exhibit anxiolytic and analgesic actions in animals. Such actions have been postulated in part to reflect effects on biogenic amine neuronal activity. Therefore the effects of gabapentin on biogenic amine neuronal activity were assessed by measuring the synthesis of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in rat brain and on the release of [3H] NE from rat hippocampal slices both in the presence and absence of the depolarizing agent 3,4-diaminopyridine (DAP). Gabapentin (30 and 100 mg/kg, i.p.) did not alter the basal synthesis rates of NE and DA as assessed by the unchanged accumulation of L-dihydroxyphenylalanine (DOPA) in the NE-enriched hippocampus and cortex and in the DA-enriched striatum and mesolimbic areas. Gabapentin also did not alter 5-HT synthesis as determined by the unaltered accumulation of 5-hydroxytryptophan (5-HTP) in the same brain areas. DAP (2 mg/kg, i.p.) induced a modest but significant increase in DOPA accumulation in the hippocampal, mesolimbic and striatal regions. This DAP-induced increase in DOPA accumulation was antagonized significantly in the hippocampus and mesolimbic regions by gabapentin at 30 and 100 mg/kg and in striatum by 100 mg/kg; a 10 mg/kg dose was inactive. DAP increased selectively 5-HT synthesis in hippocampus and this effect was blocked by gabapentin. These findings indicate that the increased synthesis of biogenic amines induced by DAP is antagonized by gabapentin. In support of the in vivo studies, gabapentin was also shown to inhibit the DAP-evoked release of [3H]NE from hippocampal slices. Although the underlying mechanism for these effects is unclear, the present findings nevertheless demonstrate that gabapentin has inhibitory effects on stimulated NE, DA and 5-HT neurons that may be involved in explaining in part the CNS effects of this drug.

4-Aminopyridine↗
PubMed1996

Effect of a high-protein meal on gabapentin pharmacokinetics.

The anticonvulsant gabapentin is transported across biological membranes via the L-amino acid transport system (System-L). Absorption of gabapentin is saturable, and in-vitro data have previously demonstrated that both L-leucine and L-phenylalanine may compete with the intestinal transport of gabapentin. The purpose of this study therefore was to determine whether a high-protein meal would interfere with gabapentin absorption. Ten healthy volunteers received in a randomized, cross-over design, a single 600-mg dose of gabapentin in the fasting state and after a high-protein meal consisting of 80 gm total protein (4.1 g phenylalanine, 8.2 g leucine and 4.2 g isoleucine), 52 g carbohydrate, and 9 g fat. Plasma gabapentin concentrations were measured by HPLC at baseline, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 30 h. Calculated pharmacokinetic parameters included Cmax' Tmax' AUC and T1/2. In addition, a pharmacodynamic assessment (using visual analog scales) of gabapentin-related adverse effects was performed at 2 h post drug ingestion and was compared between study phases. Statistical analysis included Student's t-test for paired data, with significance assigned at P < 0.05. Cmax was significantly increased by 36% (3.87 +/- 1.15 vs 5.28 +/- .97 micrograms/ml, P = 0.002), and Tmax tended to be shorter (3.9 +/- 1.8 vs 2.8 +/- .35 h, P = 0.10), after the high-protein meal. Although AUC was increased by 11%, this did not achieve statistical significance. Despite significantly higher plasma concentrations at 2 h, subjects reported significantly fewer adverse effects after the high-protein meal. Potential mechanisms to explain these unexpected findings may be that the large amino acid load delivered with the high-protein meal enhanced gabapentin absorption via trans-stimulation, the process by which acutely increased intestinal luminal amino acid concentrations result in an acute up regulation in System-L activity. Conversely, the decrease in perceived adverse CNS effects of gabapentin following the high-protein meal may reflect CNS competition for System-L transport.

Acetates↗
PubMed2005

A placebo-controlled randomized clinical trial of perioperative administration of gabapentin, rofecoxib and their combination for spontaneous and movement-evoked pain after abdominal hysterectomy.

Current treatments for post-injury movement-evoked pain are inadequate. Non-opioids may complement opioids, which preferentially reduce spontaneous pain, but most have incomplete efficacy as single agents. This trial evaluates efficacy of a gabapentin-rofecoxib combination following hysterectomy. In addition to IV-PCA morphine, 110 patients received either placebo, gabapentin (1800 mg/day), rofecoxib (50 mg/day) or a gabapentin-rofecoxib combination (1800/50 mg/day) starting 1 h pre-operatively for 72 h. Outcomes included pain at rest, evoked by sitting, peak expiration and cough, morphine consumption and peak expiratory flow (PEF). For placebo, gabapentin, rofecoxib and combination, 24 h pain (100 mm VAS) was: at rest-23.6 (P<0.05 vs. all treatments), 13.8, 14.4 and 12.1; during cough-50.7 (P<0.05 vs. all treatments), 41.5, 44.8 and 30.8; 48 h morphine consumption (mg) was: 130.4 (P<0.05 vs. all treatments), 81.7, 75.6 and 57.2 (P<0.05 vs. gabapentin and rofecoxib) and 48 h PEF (% baseline) was: 63.9 (P<0.05 vs. all treatments), 77.2, 76.7 and 87.5 (P<0.05 vs. gabapentin and rofecoxib). Adverse effects were similar in all groups except sedation which was more frequent with gabapentin. Combination and rofecoxib reduced pain interference with movement, mood and sleep (P<0.05) and combination was superior to gabapentin for all these three (P<0.05). These data suggest that a gabapentin-rofecoxib combination is superior to either single agent for postoperative pain. Other benefits include opioid sparing, reduced interference with movement, mood and sleep and increased PEF suggesting accelerated pulmonary recovery. Future research should identify optimal dose-ratios for this and other analgesic combinations.

Adult↗
PubMed1997

Gabapentin for parkinsonism: a double-blind, placebo-controlled, crossover trial.

PURPOSE: Gabapentin is a recently available anticonvulsant whose mechanism of action remains unknown. We suspected efficacy from serendipitous observations of gabapentin in patients with parkinsonism. This led us to a double-blind, placebo-controlled, crossover trial. PATIENTS AND METHODS: We administered gabapentin in a placebo-controlled, double-blind, crossover trial to 19 subjects with advanced parkinsonism. We measured the effect of placebo and gabapentin on subjects' symptoms with the Unified Parkinson's Disease Rating Scale, the Webster Scale, and the Hoehn and Yahr Scale. We assessed tremor with surface-recorded electromyography. RESULTS: Total Unified Parkinson's Disease Rating Scale improved with gabapentin compared with placebo (P = 0.0005). Likewise, activities of daily living and examination subscore of the Unified Parkinson's Disease Rating Scale improved with gabapentin compared with placebo but did not achieve statistical significance. Webster Scale showed improvement but neither Hoehn and Yahr Scale nor Webster Scale changes reached statistical significance. Tremor as measured by the Unified Parkinson's Disease Rating Scale improved with gabapentin but the use of the root mean square of the rectified electromyography as a measure of tremor activity was not statistically significant. CONCLUSIONS: This study demonstrates that gabapentin improves rigidity, bradykinesia, and tremor of parkinsonism including both Parkinson's disease and Parkinson's syndrome. The rigidity and bradykinesia of parkinsonism improve on the drug even when the effects of gabapentin on tremor are discounted.

Acetates↗
PubMed2003

Change in opioid use after the initiation of gabapentin therapy in patients with postherpetic neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is a chronic painful disorder that sometimes develops after an acute episode of herpes zoster infection (shingles) and can be difficult to treat. Although opioids are sometimes effective for chronic neuropathic pain, adverse effects are common, particularly among the elderly, and may cause many patients to discontinue therapy. OBJECTIVE: This study examined changes in opioid use after the initiation of gabapentin therapy in patients with PHN. METHODS: A health insurance claims database was used to identify all persons aged >or= 18 years who began therapy with gabapentin in 2000 or 2001 and had either (1) >or=2 medical claims with a diagnosis of PHN during the 6-month period before the first receipt of gabapentin (index date) or (2) 1 such claim or=2 prescriptions for gabapentin. RESULTS: Forty-five patients with PHN began therapy with gabapentin during the period of interest; 35 (77.8%) received >or=2 prescriptions for gabapentin. The proportion of patients receiving opioids decreased significantly between pretreatment and follow-up (from 88.9% to 71.1%; P = 0.03); the mean number of opioid prescriptions per patient also decreased significantly (from 3.9 to 3.0; P = 0.03). These reductions were observed only in patients who received >or=2 prescriptions for gabapentin; there was no significant change in opioid use among those who received only 1 prescription for gabapentin. CONCLUSION: In this study, initiation of gabapentin therapy in patients with PHN was associated with a reduction in the use of opioid analgesics.

Acetates↗