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

Chen, Chao

doi:10.1007/s00228-013-1545-1

Cited by 15 publications

(14 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, the bioavailability of carbamazepine is considered to be 80% on average, but ranges considerably [72]. In the case of gabapentin, bioavailability is inversely proportional to the taken dose, resulting in reduced increases in exposure with increasing doses [73]. Finally, absorption and first-pass metabolism can be influenced by food intake and beverages, such as grapefruit juice [74].…”

Section: Drug-food Interaction and Formulation Variabilitymentioning

confidence: 99%

Pharmacotherapy in pediatric epilepsy: from trial and error to rational drug and dose selection – a long way to go

Dijkman

Álvarez-Jiménez

Danhof

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

Introduction: Whereas ongoing efforts in epilepsy research focus on the underlying disease processes, the lack of a physiologically based rationale for drug and dose selection contributes to inadequate treatment response in children. In fact, limited information on the interindividual variation in pharmacokinetics and pharmacodynamics of anti-epileptic drugs (AEDs) in children drive prescription practice, which relies primarily on dose regimens according to a mg/kg basis. Such practice has evolved despite advancements in pediatric pharmacology showing that growth and maturation processes do not correlate linearly with changes in body size. Areas covered: In this review we aim to provide 1) a comprehensive overview of the sources of variability in the response to AEDs, 2) insight into novel methodologies to characterise such variation and 3) recommendations for treatment personalisation. Expert opinion: The use of pharmacokinetic-pharmacodynamic principles in clinical practice is hindered by the lack of biomarkers and by practical constraints in the evaluation of polytherapy. The identification of biomarkers and their validation as tools for drug development and therapeutics will require some time. Meanwhile, one should not miss the opportunity to integrate the available pharmacokinetic data with modeling and simulation concepts to prevent further delays in the development of personalised treatments for pediatric patients.

show abstract

Section: Drug-food Interaction and Formulation Variabilitymentioning

confidence: 99%

Pharmacotherapy in pediatric epilepsy: from trial and error to rational drug and dose selection – a long way to go

Dijkman

Álvarez-Jiménez

Danhof

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

show abstract

“…Gabapentin is removed from the plasma by hemodialysis, and thus, the drug is not recommended for patients with RLS receiving hemodialysis 28. Recently, a meta-analysis of dose–exposure relationships for gabapentin after oral administration of gabapentin and gabapentin enacarbil was reported 49. The study collected published pharmacokinetic data for gabapentin and gabapentin enacarbil from 35 identified studies conducted in at least 192–497 subjects.…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…The AUC of gabapentin after a gabapentin enacarbil 700 mg dose (53.0 μg hour/mL) was also comparable to the gabapentin AUC (56.6 μg hour/mL) after a gabapentin dose of 1,200 mg/day, a standard antiepilepsy dose 69. A recent meta-analysis study of 35 pharmacokinetic studies on gabapentin and gabapentin enacarbil included an accurate conversion graph of the two drugs and suggested that the therapeutic effects of 900 to 1,800 mg of gabapentin were comparable to the same dose range of gabapentin enacarbil 49. If this is correct, one can apply the safety data of gabapentin to gabapentin enacarbil at least by 1,800 mg/day and confidently reduce the potential risk for pancreatic acinar cell tumor in patients treated with gabapentin enacarbil, similar to that with gabapentin.…”

Section: Benefit–risk Assessmentmentioning

confidence: 99%

“…The clinical significance of RLS has also emerged through various clinical research studies including gabapentin enacarbil trials and several epidemiological studies 50,70,71. Huge amounts of pharmacokinetic data have been collected on gabapentin enacarbil, and more accurate pharmacokinetic profiles have been published,49 which may allow extrapolation of the 15-year gabapentin experience to the new treatment with gabapentin enacarbil.…”

Section: Benefit–risk Assessmentmentioning

confidence: 99%

See 1 more Smart Citation

Gabapentin enacarbil for the treatment of moderate to severe primary restless legs syndrome (Willis-Ekbom disease): 600 or 1,200 mg dose?

Kume¹

2014

NDT

View full text Add to dashboard Cite

Gabapentin enacarbil is a prodrug of the anticonvulsant gabapentin. The efficacy and safety of gabapentin enacarbil for the treatment of moderate to severe primary restless legs syndrome (RLS) has been evaluated in several clinical trials in the United States and Japan. Although most clinical trials assessed gabapentin enacarbil at doses greater than 600 mg/day and demonstrated the overall safety and efficacy (defined as improvements in the coprimary endpoints of the international RLS rating scale [IRLS] total score and Clinical Global Impression-Improvement response), the US Food and Drug Administration approved the 600 mg once-daily dosage because doses higher than 600 mg/day were considered to provide no additional benefits and were associated with higher rates of adverse events, such as somnolence and dizziness. Nonetheless, the results of clinical trials and post hoc meta-analyses have indicated that the 1,200 mg once-daily dosage was the most validated gabapentin enacarbil treatment for not only subjective RLS symptoms but also severe sleep disturbance associated with RLS. A Japanese dose-finding study showed that 900 mg/day, the intermediate dose between 600 and 1,200 mg, failed to show a significant improvement in IRLS total score, probably because many of the patients who discontinued treatment did so early, suggesting that a half-landing dose may cause more adverse effects than favorable ones in some RLS patients early in the treatment. Gabapentin enacarbil may have two distinct therapeutic doses for the treatment of RLS: 600 mg/day or lower doses for the treatment of subjective RLS symptoms and 1,200 mg/day or higher doses for the treatment of both subjective RLS symptoms and associated problems such as severe sleep disturbances.

show abstract

“…The bioavailability of GBP is inversely proportional to the dose: 60% at 900 mg/day and 27% at 4800 mg/day (administered in three divided doses) [76] . In contrast, its prodrug, enacarbil, showed essentially linear dose-proportional pharmacokinetic properties [77,78] . GBP has a volume of distribution of 58 L after 150 mg intravenous administration [76] .…”

Section: Gabapentin (Gbp)mentioning

confidence: 99%

Alleviation of pain in painful diabetic neuropathy

Tajti

Delia

Majláth

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

Introduction: Painful diabetic neuropathy (PDN) is a disabling pain condition. Its pathomechanism remains unknown, but a sensitization and neuronal hyperexcitabilty have been suggested. Only symptomatic pharmacological pain-alleviation treatment is currently available. Areas covered:The origin of PDN is enigmatic, and the evidence-based therapeutic guidelines therefore consist only of antidepressants and antiepileptics as first-line recommended drugs. This article relates to a MEDLINE/PubMed systematic search (2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015). Expert opinion:The results of the meta-analysis from the aspect of the efficacy of amitriptyline, duloxetine, venlafaxine, gabapentin and pregabalin are favorable, but the placebo response rate is relatively high in patients with neuropathic pain. For personalization of the medication of PDN patients, the optimum dosing, the genotyping of the metabolizing enzymes and optimum biomarkers are needed. As concerns the future perspectives, specific sodium channel subtype inhibitors acting on peripheral nociceptive neurons or modified Ttype voltage-gated calcium channel blockers may be promising targets for pharmaceutical innovations. Another attractive strategy for the treatment is based on the effects of monoclonal antibodies against nerve growth factor, sodium channel, specific receptor and cytokines. Botulinum toxin A, capsaicin patch and spinal cord stimulation therapies are the nearest future therapeutic options for the treatment of PDN patients.

show abstract

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

Cited by 15 publications

References 24 publications

Pharmacotherapy in pediatric epilepsy: from trial and error to rational drug and dose selection – a long way to go

Pharmacotherapy in pediatric epilepsy: from trial and error to rational drug and dose selection – a long way to go

Gabapentin enacarbil for the treatment of moderate to severe primary restless legs syndrome (Willis-Ekbom disease): 600 or 1,200 mg dose?

Alleviation of pain in painful diabetic neuropathy

Contact Info

Product

Resources

About