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Gabapentin: profile and news
PDI sees red after plummeting profit; loss of biggest client 07 Mar 2006 AstraZeneca lodges appeal in Toprol XL patent case Feb 16, 2006 AstraZeneca launches Toprol-XL appeal Feb 17, 2006 Toprol XL uncertainty weighs heavy on AstraZeneca Feb 3, 2006 AstraZeneca Sees Slower Earnings Growth on Toprol-XL (Update4) Feb 2, 2006 AstraZeneca Forecasts Slower Growth on Toprol-XL (Update1) Feb 2, 2006 UPDATE 1-AstraZeneca profit leaps, Toprol key to 2006 Feb 2, 2006 AstraZeneca Down On Toprol Concern -Traders Feb 2, 2006 Drug marketer PDI loses $19.7M in fourth quarter Mar 3, 2006 AstraZeneca NXY059 Data Not Price Sensitive Feb 23, 2006 AZ withdraws Exanta from world market Feb 14, 2006 AstraZeneca: the clot thickens Feb 16, 2006 Drug firm stock falls despite big profit gain Feb 3, 2006 AstraZeneca files appeal over heart drug patent Feb 16, 2006 ABN Amro Downgrades AstraZeneca To Hold Feb 3, 2006 AstraZeneca "buy," estimates raised Feb 3, 2006 AstraZeneca Hopes to Hold Off Generics Feb 2, 2006 Strong earnings for AstraZeneca, but more legal woes Feb 2, 2006 2005 banner year for AstraZeneca Feb 3, 2006 UPDATE 2-Heart drug clouds AstraZeneca prospects for 2006 Feb 2, 2006 Copycat drug fears a drag on AstraZeneca Feb 2, 2006 AstraZeneca 4Q earnings jump 32 percent Feb 2, 2006 AZ admits Exanta will never be cleared for sale in US pharmacies Feb 2, 2006 AstraZeneca dragged down by heart drug fears Feb 2, 2006 AstraZeneca profit climbs 32% but shares slip Feb 2, 2006 AstraZeneca 4th-Qtr Profit Rises 33% on Seroquel (Update1) Feb 2, 2006 AstraZeneca annual results in line, sees double-digit growth in ... Feb 2, 2006 Astra makes new drugs its top priority Feb 2, 2006 AstraZeneca annual results in line UPDATE Feb 2, 2006 AstraZeneca Profit Boom Feb 2, 2006 AstraZeneca Fourth-Quarter Profit Grows Feb 2, 2006 AstraZeneca 4Q A Mixed Bag - Collins Stewart Feb 2, 2006 AstraZeneca clawed by copycats Feb 2, 2006 Seymour Pierce Still Bearish On AstraZeneca Feb 3, 2006 AstraZeneca profit climbs 32% Feb 2, 2006 AstraZeneca: Of Patents and Pipelines Feb 2, 2006 KV Pharmaceutical Reports Record Revenues for Fiscal 2006 Third ... Feb 7, 2006 AstraZeneca Q4 net profits up 32% Feb 2, 2006 Thursday's preview: AstraZeneca, Royal Dutch Shell Feb 1, 2006 AstraZeneca FY Solid, In Line - Lehman Feb 2, 2006 We're cutting back on our credit card debt Feb 1, 2006 Generics Erosion will Result in Slow Growth of Market to Treat ... Feb 1, 2006 European Stocks Decline After US Jobs Report; Volvo Drops Feb 3, 2006 US Drug Shares, Beaten in 2005, May Trail European Rivals Feb 5, 2006 AstraZeneca abandons blood thinner, citing risk Feb 15, 2006 A Brief Closing Market Feb 3, 2006 Burning Questions Feb 9, 2006 Rob Gordon, Charlotte Roy Join Harrington Group Feb 16, 2006 Other information Indication For the management of postherpetic neuralgia in adults and as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in patients over 12 years of age with epilepsy Pharmacology Gabapentin, an analog of GABA, is used as an anticonvulsant to treat partial seizures, amyotrophic lateral sclerosis (ALS), and painful neuropathies. Potential uses include monotherapy of refractory partial seizure disorders, and treatment of spasticity in multiple sclerosis, tremor. mood disorders, and attenuation of disruptive behaviors in dementia. Gabapentin has high lipid solubility, is not metabolized by the liver, has no protein binding, and doesn't possess the usual drug interactions. Mechanism Of Action Gabapentin interacts with cortical neurons at auxillary subunits of voltage-sensitive calcium channels. Gabapentin increases the synaptic concentration of GABA, enhances GABA responses at non-synaptic sites in neuronal tissues, and reduces the release of mono-amine neurotransmitters. One of the mechanisms implicated in this effect of gabapentin is the reduction of the axon excitability measured as an amplitude change of the presynaptic fibre volley (FV) in the CA1 area of the hippocampus. This is mediated through its binding to presynaptic NMDA receptors. Other studies have shown that the antihyperalgesic and antiallodynic effects of gabapentin are mediated by the descending noradrenergic system, resulting in the activation of spinal alpha2-adrenergic receptors. Gabapentin has also been shown to bind and activate the adenosine A1 receptor. Drug Category Antimanic Agents; Anti-anxiety Agents; Antiparkinson Agents; Antidyskinetics; Analgesics; Anticonvulsants; ATC:N03AX12 Brand Names/Synonyms Aclonium; Gababentin; Gabapentin; Gabapentin [Usan:Ban:Inn]; Gabapentine; Gabapentine [Inn-French]; Gabapentino [Inn-Spanish]; Gabapentino [Spanish]; Gabapentinum [Inn-Latin]; Gabapetin; Neurontin; Novo-Gabapentin Dosage Forms Oral tablets and oral Solution Absorption 60%, 47%, 34%, 33%, and 27% following 900, 1200, 2400, 3600, and 4800 mg/day given in 3 divided doses, respectively. Interactions -->Interactions for Gabapentin: In vitro studies were conducted to investigate the potential of gabapentin to inhibit the major cytochrome P450 enzymes (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) that mediate drug and xenobiotic metabolism using isoform selective marker substrates and human liver microsomal preparations. Only at the highest concentration tested (171 μg/mL; 1 mM) was a slight degree of inhibition (14%-30%) of isoform CYP2A6 observed. No inhibition of any of the other isoforms tested was observed at gabapentin concentrations up to 171 mg/mL (approximately 15 times the Cmax at 3600 mg/day). Gabapentin is not appreciably metabolized nor does it interfere with the metabolism of commonly coadministered antiepileptic drugs. The drug interaction data described in this section were obtained from studies involving healthy adults and adult patients with epilepsy. Phenytoin: In a single (400 mg) and multiple dose (400 mg TID) study of NeurontinÒ in epileptic patients (N=8) maintained on phenytoin monotherapy for at least 2 months, gabapentin had no effect on the steady-state trough plasma concentrations of phenytoin and phenytoin had no effect on gabapentin pharmacokinetics. Carbamazepine: Steady-state trough plasma carbamazepine and carbamazepine 10, 11 epoxide concentrations were not affected by concomitant gabapentin (400 mg TID; N=12) administration. Likewise, gabapentin pharmacokinetics were unaltered by carbamazepine administration. Valproic Acid: The mean steady-state trough serum valproic acid concentrations prior to and during concomitant gabapentin administration (400 mg TID; N=17) were not different and neither were gabapentin pharmacokinetic parameters affected by valproic acid. Phenobarbital: Estimates of steady-state pharmacokinetic parameters for phenobarbital or gabapentin (300 mg TID; N=12) are identical whether the drugs are administered alone or together. Naproxen: Coadministration (N=18) of naproxen sodium capsules (250 mg) with NeurontinÒ (125 mg) appears to increase the amount of gabapentin absorbed by 12% to 15%. Gabapentin had no effect on naproxen pharmacokinetic parameters. These doses are lower than the therapeutic doses for both drugs. The magnitude of interaction within the recommended dose ranges of either drug is not known. Hydrocodone: Coadministration of NeurontinÒ (125 to 500 mg; N=48) decreases hydrocodone (10 mg; N=50) Cmax and AUC values in a dose-dependent manner relative to administration of hydrocodone alone; Cmax and AUC values are 3% to 4% lower, respectively, after administration of 125 mg NeurontinÒ and 21% to 22% lower, respectively, after administration of 500 mg NeurontinÒ. The mechanism for this interaction is unknown. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses is not known. Morphine: A literature article reported that when a 60-mg controlled-release morphine capsule was administered 2 hours prior to a 600-mg NeurontinÒ capsule (N=12), mean gabapentin AUC increased by 44% compared to gabapentin administered without morphine. Morphine pharmacokinetic parameter values were not affected by administration of NeurontinÒ 2 hours after morphine. The magnitude of interaction at other doses is not known. Cimetidine: In the presence of cimetidine at 300 mg QID (N=12) the mean apparent oral clearance of gabapentin fell by 14% and creatinine clearance fell by 10%. Thus cimetidine appeared to alter the renal excretion of both gabapentin and creatinine, an endogenous marker of renal function. This small decrease in excretion of gabapentin by cimetidine is not expected to be of clinical importance. The effect of gabapentin on cimetidine was not evaluated. Oral Contraceptive: Based on AUC and half-life, multiple-dose pharmacokinetic profiles of norethindrone and ethinyl estradiol following administration of tablets containing 2.5 mg of norethindrone acetate and 50 mcg of ethinyl estradiol were similar with and without coadministration of gabapentin (400 mg TID; N=13). The Cmax of norethindrone was 13% higher when it was coadministered with gabapentin; this interaction is not expected to be of clinical importance. Antacid (MaaloxÒ): Maalox reduced the bioavailability of gabapentin (N=16) by about 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after Maalox. It is recommended that gabapentin be taken at least 2 hours following Maalox administration. Effect of Probenecid: Probenecid is a blocker of renal tubular secretion. Gabapentin pharmacokinetic parameters without and with probenecid were comparable. This indicates that gabapentin does not undergo renal tubular secretion by the pathway that is blocked by probenecid. Drug/Laboratory Tests Interactions Because false positive readings were reported with the Ames N-Multistix SGÒ dipstick test for urinary protein when gabapentin was added to other antiepileptic drugs, the more specific sulfosalicylic acid precipitation procedure is recommended to determine the presence of urine protein. |
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