Oral Administration Of Gabapentin Research Articles

Effects of gabapentin and trazodone on electroretinographic responses in clinically normal dogs.

To compare electroretinographic (ERG) responses obtained in dogs before and after oral administration of gabapentin, trazodone, and a combination of both medications. 12 clinically normal dogs. A short-protocol ERG with 20 minutes of dark adaption was recorded for all dogs to establish baseline ERG responses. Dogs then received gabapentin (approx 30 mg/kg), trazadone (approx 20 mg/kg or approx 5 mg/kg), or a combination of gabapentin (approx 20 mg/kg) and trazodone (approx 5 mg/kg) orally, and the same ERG protocol was repeated 2 hours later. Dogs were given a washout period of at least 1 week between treatments. a-Wave amplitudes were significantly (P = 0.018) decreased after administration of the combination of gabapentin and trazodone. b-Wave amplitudes were significantly decreased after administration of the 20-mg/kg dose of trazodone (P = 0.006) and after administration of the combination of gabapentin and trazodone (P = 0.002). Heavier dogs that received higher total doses of trazodone had decreases in a-wave amplitude after administration of the 20-mg/kg dose of trazodone and in b-wave amplitude after administration of the 5-mg/kg dose of trazodone. High doses of trazodone and the combination of gabapentin and trazodone significantly decreased a-wave and b-wave amplitudes in clinically normal dogs. However, the effects on retinal responses had little clinical importance. Therefore, these medications can be used safely in a clinical setting; however, further studies are needed in dogs with retinal disease.

Pharmacokinetic Profiles of Gabapentin after Oral and Subcutaneous Administration in Black-tailed Prairie Dogs (Cynomys ludovicianus).

In veterinary and human medicine, gabapentin (a chemical analog of γ-aminobutyric acid) is commonly prescribed to treat postoperative and chronic neuropathic pain. This study explored the pharmacokinetics of oral and subcutaneous administration of gabapentin at high (80 mg/kg) and low (30 mg/kg) doses as a potential analgesic in black-tailed prairie dogs (Cynomys ludovicianus; n = 24). The doses (30 and 80 mg/kg) and half maximal effective concentration (1.4 to 16.7 ng/mL) for this study were extrapolated from pharmacokinetic efficacy studies in rats, rabbits, and cats. Gabapentin in plasma was measured by using an immunoassay, and data were evaluated using noncompartmental analysis. The peak plasma concentrations (mean ±1 SD) were 42.6 ±14.8 and 115.5 ±15.2 ng/mL, respectively, after 30 and 80 mg/kg SC and 14.5 ±3.5 and 20.7 ±6.1 ng/mL after the low and high oral dosages, respectively. All peak plasma concentrations of gabapentin occurred within 5 h of administration. Disappearance half-lives for the low and high oral doses were 7.4 ± 6.0 h and 5.0 ± 0.8 h, respectively. The results of this study demonstrate that oral administration of gabapentin at low (30 mg/kg) doses likely would achieve and maintain plasma concentrations at half maximum effective concentration for 12 h, making it a viable option for an every 12-h treatment.

Comparison of therapeutic effects of continuous epidural nerve block combined with drugs on postherpetic neuralgia

Purpose To compare the therapeutic effects of continuous epidural block combined with drugs and oral drugs alone on postherpetic neuralgia (PHN). Methods Ninety-six PHN patients meeting the standard were selected and divided into group A and group B. Patients in group A had epidural block combined with oral administration of gabapentin and oxycodone-acetaminophen, and patients in group B received oral gabapentin and oxycodone-acetaminophen. Visual analogue scale (VAS) and Wisconsin brief pain inventory scores were used to evaluate the patients in group A and group B for 6 times (before treatment, 1 d, 3 d, 7 d, 15 d and 30 d after treatment) respectively, and the complications and adverse reactions of the two treatment methods, as well as the number of cases requiring remedial measures were observed. Results There were significant differences in VAS and Wisconsin brief pain inventory scores at 1 d, 3 d, 7 d, 15 d and 30 d after treatment between the two groups (p < 0.05). Moreover, the scores before and after treatment decreased with the time of treatment, and there was a significant difference between the two groups at different time points (p < 0.05). No significant adverse reactions were observed in group A except for 1 patient with catheter detachment. Compared with group A, the adverse reactions of group B were more varied and obvious. Conclusion Both treatments have certain effects on PHN, but epidural block combined with drug therapy is more effective, especially for patients with severe pain, early use can quickly relieve pain.

Clinical observations on selective dorsal root ganglion pulsed radiofrequency lesioning combined with gabapentin in the treatment of postherpetic neuralgia.

This study investigated the clinical effects of selective dorsal root ganglion pulsed radiofrequency lesioning in combination with oral administration of gabapentin in the treatment of postherpetic neuralgia (PHN). One hundred and sixteen consecutive cases of initially diagnosed patients with PHN were randomly divided into the control and the observation groups, with each group consisting of 58 patients. The control group was treated with oral gabapentin (2400 mg/d, tid), while the observation group received gabapentin and pulsed radiofrequency lesioing of the dorsal root ganglion. The clinical efficacy of both the regimens was compared after a follow up period of 6 months. The observation group had a significantly lower score on the visual analog scale than the control group (P ≤ 0.05, with no significant complications occurring in both the groups) at a 1, 2, and 4 week posttreatment duration. The percentage of cluster of differentiation (CD) 4+ cells and the CD4+/CD8+ ratio increased gradually, while the percentage of CD8 + cells decreased in the observation group (P ≤ 0.05). No significant alterations were observed in the control group (P > 0.05). The observation group had significantly lower serum interleukin-6, C-reactive protein, and tumor necrosis factor-α levels than the control group (P < 0.05) at 1, 2, and 4 weeks after the treatment was instituted. The observation group also demonstrated a superior total effective rate and efficiency than the control group (P ≤ 0.05). Our study demonstrated that radiofrequency combined with gabapentin in the treatment of PHN has a good safety and efficacy profile. The effects of this treatment may be related to an increased T-cell immunity and an inhibited inflammatory response.

Effects of premedication with oral gabapentin on intraocular pressure changes following tracheal intubation in clinically normal dogs

BackgroundGabapentin is an antiepileptic drug widely approved as an add-on therapy for epilepsy treatment in human and dogs. There is a clinical impression that gabapentin is a suitable drug which attenuates the IOP elevation associated with tracheal intubation in humans. The present study performed to determine the effects of oral gabapentin on intraocular pressure (IOP) changes following tracheal intubation in dogs.ResultsTwenty adult healthy dogs were randomly assigned to treatment (n = 10) and control (n = 10) groups. Dogs in the treatment group received oral gabapentin (50 mg/kg) 2 h before induction of anesthesia and dogs in the control group received oral gelatin capsule placebo at the same time. The dogs were anesthetized with propofol 6 mg/kg, and anesthesia was maintained with a constant infusion of 0.2 mg/kg/min of propofol for 20 min. IOP were measured immediately before induction and then repeated immediately after induction, as well as 5 min, 10 min and 15 min following tracheal intubation in both groups. IOP was significantly higher immediately after induction, and 5 min after tracheal intubation when compared with IOP reading before induction in the control group. There was no statistically significant change in IOPs immediately after induction, and 5 min after tracheal intubation in comparison to the values before induction in the treatment group.ConclusionsBased on the findings of this study, preanesthetic oral administration of gabapentin significantly prevents an increase in the IOP associated with tracheal intubation in dogs anesthetized with propofol.

Analgesic synergism of gabapentin and carbamazepine in rat model of diabetic neuropathic pain

Purpose: To evaluate synergy in the analgesic effects of a combination therapy of carbamazepine (CBZ) and gabapentin (GBP) in diabetic neuropathic pain.Methods: Neuropathic pain was produced in rats by a single intraperitoneal injection of streptozotocin (STZ) at 60 mg/kg. CBZ, GBP, and their combination were orally administered at varying doses (GBP 30 - 180 mg/kg; CBZ 20 - 40 mg/kg) comparable to their therapeutic doses in humans. Nociceptive responses in the diabetic rats were assessed using hot plate test.Results: Hot plate latency significantly increased with oral administration of GBP at a dose of 180 mg/kg when compared with control group (p &lt; 0.05), while at a dose of 90 mg/kg, the increase was not significant. Oral administration of CBZ at doses of 20 and 40 mg/kg did not produce any significant impact on hot plate latency. However, a combination of GBP at 90 mg/kg and CBZ at 20 mg/kg produced significant increase in latency, compared with control group and other groups (p &lt; 0.05), except the group that received 180 mg/kg GBP. The combination of low dose GBP 30 mg/kg and carbamazepine 30 mg/kg had no significant effect on latency (p &gt; 0.05).Conclusion: The results obtained in this study provide useful information on the combination therapy of GBP and CBZ, which may be applied in the treatment of pain in diabetic neuropathy.Keywords: Diabetic neuropathy, Carbamazepine, Gabapentin, Hot-plate test

Meta-analyses of dose-exposure relationships for gabapentin following oral administration of gabapentin and gabapentin enacarbil

Gabapentin exposure following administration of certain doses of gabapentin or its pro-drug gabapentin enacarbil has been previously reported in the literature, with variable results. Meta-analyses of dose-exposure relationships were conducted to maximise precision and minimise bias. Study-level mean data for gabapentin systemic exposure, in terms of bioavailable dose and steady-state average plasma concentration, were modelled as a function of daily dose. Several linear and non-linear candidate models were tested. An Emax model best described the dose-exposure relationships for gabapentin. The ED50 was 3,080 mg/day for bioavailable dose or 3,370 mg/day for steady-state concentration; and the maximum exposure was 2,340 mg/day or 16.9 mg/L. For gabapentin enacarbil, a power model was most suitable, with a power of 0.925 for bioavailable dose or 0.844 for steady-state concentration. All parameters were estimated with < 20 % standard error. Simulations confirmed that these models accurately reflected the distribution of the respective data, and bootstrapping showed high precision for the estimated dose-exposure curves. The meta-analyses addressed issues associated with between-study variability; and confirmed the highly non-linear nature of dose-exposure relationships for gabapentin and the essentially linear relationships for gabapentin enacarbil. The resulting models could be used to simulate exposure at any clinically relevant dose and bridge therapeutic dose range between the two drugs.

The Importance of Perioperative Administration of an Anti-Hyperalgesic Drug in Burn Wounds

Dear Editor, We read with interest the article by Rimaz and coworkers about the beneficial effect of preoperative oral administration of a high single dose (1200 mg) of gabapentin on postoperative pain scores and morphine consumption in patients undergoing surgical debridement of burn wounds (1). The effect of preoperative administration of oral gabapentin in order to reduce postoperative pain scores and opioid consumption was analyzed in several studies. A systematic review of randomized controlled trials published by Ho and coworkers has shown that, in different types of surgery, the preoperative administration of a single dose of 1200 mg oral gabapentin produced a significant reduction in pain intensity at rest compared with placebo in the early and late postoperative period at 6 and 24 h after administration, respectively. In addition, some similar studies showed a significant reduction in opioid consumption and a delayed request for analgesia (2). As regard to the adverse effects, the administration of 1200 mg of oral gabapentin did not show significant differences with respect to placebo in a large part of published studies. Indeed, as highlighted by Turan and coworkers, the treatment group showed fewer episodes of vomiting and urinary retention, probably due to lower consumption of opioids in the postoperative period (3). However, administration of a single dose of 1200 mg of oral gabapentin in the preoperative period showed no serious adverse effects in the treated patients. The analysis of available data has revealed a number of limitations, in particular due to the different type of surgery. An interesting systematic review published by Mathiesen et al. focused on the use of gabapentin in the preoperative period in relation to the surgical procedures. Reported data showed that preoperative gabapentin administration in different dosages appears to be particularly effective in reducing postoperative opioid consumption particularly after abdominal hysterectomy and spinal surgery, while the use in other sort of surgeries revealed no significant results. In addition, a reduction in pain scores was demonstrated mostly in early postoperative period, probably due to higher gabapentin plasmatic level in the early postoperative phase (4). At a single preoperative oral dose of 1200 mg, gabapentin showed conflicting results in relation to different types of surgeries, with promising evidences only in abdominal hysterectomy, spinal surgery, radical mastectomy, thyroid and ear-nose throat surgery. However, these results should be confirmed by further investigations using the same methodology, in particular with respect to the type of anesthesia and rescue analgesia in the postoperative period. Currently, there are no other publications on the use of preoperative gabapentin in postoperative pain in burned patients. In this regard, we agree with the authors that the burn wounds, in relation to the particular type of damage, may benefit from perioperative administration of an anti-hyperalgesic drug. In fact, some nerve endings of skin nociceptors after burns are still intact or only partially injured and continue to generate pain impulses leading to primary hyperalgesia (5). However, further studies are needed to confirm these results, especially focused on the dose-response relationship of preoperative gabapentin, looking for the lowest effective dose.

Preoperative use of gabapentin decreases the anesthetic and analgesic requirements in patients undergoing radical mastectomy

Background/aimGabapentin is an anticonvulsant drug that is safe and effective for the treatment of neuropathic pain syndrome, as well as postoperative pain with good results. This prospective randomized study was done to evaluate the effects of preoperative administration of oral gabapentin (1200 mg) on the intraoperative fentanyl and isoflurane consumption, postoperative analgesic requirements and postoperative pain in patients undergoing radical mastectomy.MethodsSixty ASA I and II patients were randomly allocated into two equal groups to receive oral gabapentin 1200 mg, 2 h before surgery (G group) or control (C group). General anesthesia was induced and maintained at bispectral index value between 40 and 60. During surgery the end-tidal isoflurane concentrations required to maintain adequate depth of anesthesia and the required incremental doses of intraoperative fentanyl were recorded. Postoperative pain was assessed using visual analogue scale (VAS) at rest for 24 h. Postoperatively, whenever visual analogue scale (VAS) was more than 5 or on patients’ demand, analgesia in both groups was provided with diclofenac sodium (1 mg/kg IM) or tramadol hydrochloride (1 mg/kg IV) as needed. VAS, analgesics requirements, and side-effects were assessed for 24 h postoperatively.ResultsIntraoperative fentanyl and postoperative analgesic consumption were significantly lower in G group than C group (P < 0.001). Patients in the G group had significantly lower end-tidal concentrations of isoflurane required to maintain adequate depth of anesthesia (P < 0.05). VAS was significantly lower in G group than C group at the first three measurement times (P < 0.01). The incidence of postoperative nausea and vomiting was significantly lower in G group than C group (30% versus 60% of patients, respectively, P < 0.05). The incidence of dizziness was significantly higher in the G group than C group (26% versus 3.3% of patients, respectively, P < 0.05).ConclusionGabapentin (1200 mg) administered orally 2 h before surgery decreased the intraoperative fentanyl and isoflurane consumption, postoperative analgesic requirements, postoperative pain, and the incidence of postoperative nausea and vomiting, but increased dizziness.

Efficacy of Gabapentin for Radiculopathy Caused by Lumbar Spinal Stenosis and Lumbar Disk Hernia

The efficacy of gabapentin monotherapy was investigated against both acute or chronic radicular pain caused by lumbar disk hernia (LDH) or lumbar spinal stenosis (LSS). Seventy-eight patients with radicular pain, 10 males and 68 females aged 23 to 76 years (mean 49.4 years), caused by LSS in 45 patients or LDH in 33 patients were treated with oral administration of gabapentin and were followed up for 3 months. The evaluation included neurological examination, Odom's criteria, visual analog pain scale (VAS), and walking distance. Gabapentin treatment resulted in decreased VAS scores in both groups. Odom's criteria scores had improved to excellent or good in 36 patients with LSS and 28 patients with LDH. Furthermore, walking distance was significantly longer at the 3rd month of the treatment protocol. Eight patients discontinued gabapentin therapy because of the side effects. Gabapentin could be an option in the conservative management of acute or chronic radicular pain.

Mechanical Allodynia Induced by Paclitaxel, Oxaliplatin and Vincristine: Different Effectiveness of Gabapentin and Different Expression of Voltage-Dependent Calcium Channel .ALPHA.2.DELTA.-1 Subunit

We compared the inhibitory action of gabapentin, which is used to treat neuropathic pain, on mechanical allodynia induced by chemotherapeutic agents, paclitaxel, oxaliplatin, and vincristine, in mice. Single injections of paclitaxel, oxaliplatin, and vincristine at the doses corresponding to doses clinically used caused mechanical allodynia of similar intensity. Oral administration of gabapentin (30, 100 mg/kg) produced a dose-dependent inhibition of allodynia caused by paclitaxel and oxaliplatin, but not vincristine. Intrathecal injection of gabapentin (30, 100microg/site) significantly inhibited allodynia induced by paclitaxel, but not oxaliplatin and vincristine. Intraplantar injection of gabapentin (30, 100 microg/site) did not significantly inhibit allodynia induced by paclitaxel and oxaliplatin. Paclitaxel increased the expression of mRNA of voltage-dependent calcium channel alpha(2)delta-1 subunit, an action site of gabapentin, in the dorsal spinal cord, and oxaliplatin increased it in the dorsal root ganglia. Vincristine was without effects on alpha(2)delta-1 subunit mRNA in these regions. These results suggest that the efficacy of gabapentin in the treatment of mechanical allodynia is dependent on chemotherapy agent used. It may be partly due to the distinct effects of chemotherapy agents on the expression of alpha(2)delta-1 subunit of voltage-dependent calcium channel.

Synergistic antiallodynic interaction between gabapentin or carbamazepine and either benfotiamine or cyanocobalamin in neuropathic rats

Anticonvulsants, including gabapentin and carbamazepine, have shown activity against several types of neuropathic pain; however, they have limiting side effects that may minimize their use. In this study the possible synergistic interaction between anticonvulsants and benfotiamine or cyanocobalamin on spinal nerve ligation-induced tactile allodynia was assessed. Oral administration of gabapentin (15-300 mg/kg), carbamazepine (10-300 mg/kg), benfotiamine (30-600 mg/kg) or cyanocobalamin (0.3-6.0 mg/kg) significantly reduced tactile allodynia in rats. Maximal antiallodynic effects were reached with gabapentin 300 mg/kg (approximately 70%), carbamazepine 300 mg/kg (approximately 66%), benfotiamine 600 mg/kg (approximately 51%) and cyanocobalamin 6 mg/kg (approximately 59%). At the highest tested doses, gabapentin, but not carbamazepine, benfotiamine or cyanocobalamin, significantly reduced motor coordination. Coadministration of gabapentin or carbamazepine with benfotiamine or cyanocobalamin in a fixed ratio markedly reduced spinal nerve ligation-induced tactile allodynia, showing a synergistic interaction between anticonvulsants and B vitamins. Data indicate that combinations of anticonvulsants with benfotiamine or cyanocobalamin are able to reduce tactile allodynia without affecting motor coordination in rats, and suggest the possible clinical use of these combinations in the treatment of neuropathic pain in humans.

161 Attenuation of formalin-induced nociceptive behaviors following oral administration of gabapentin and pregabalin

161 Attenuation of formalin-induced nociceptive behaviors following oral administration of gabapentin and pregabalin

Gabapentin treatment of multiple piloleiomyoma-related pain

Familial leiomyomatosis cutis et uteri may present with numerous cutaneous leiomyomas, or piloleiomyomas, which can be painful. Pharmacologic agents have had limited efficacy in mitigating leiomyoma-associated discomfort. We describe a case of familial piloleiomyomas in which intermittent pain at the site of the lesions was substantially reduced by the administration of oral gabapentin. The unusual unilateral distribution of leiomyomas in this case is discussed. (J Am Acad Dermatol 2002;46:S27-9.)