SynthesisEuropean journal of clinical pharmacology2013
Meta-analyses of dose-exposure relationships for gabapentin following oral administration of gabapentin and gabapentin enacarbil.
Synthesis in European journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
4 citing papers in PubMed.
- Interindividual Variability in the Bioavailability of Gabapentin Enacarbil Extended Release in Healthy Adults: An Analysis of Data From 6 Phase I Studies.Therapeutic drug monitoring · 2022Article
- Application of Pharmacokinetics and Pharmacodynamics in Product Life Cycle Management. A Case Study with a Carbidopa-Levodopa Extended-Release Formulation.The AAPS journal · 2017Review
- Dose-related beneficial and harmful effects of gabapentin in postoperative pain management - post hoc analyses from a systematic review with meta-analyses and trial sequential analyses.Journal of pain research · 2017Review
- Gabapentin enacarbil for the treatment of moderate to severe primary restless legs syndrome (Willis-Ekbom disease): 600 or 1,200 mg dose?Neuropsychiatric disease and treatment · 2014Review
Corrections and comments
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Authors and funding
1 author.
Funding
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Abstract
backgroundGabapentin exposure following administration of certain doses of gabapentin or its pro-drug gabapentin enacarbil has been previously reported in the literature, with variable results.
methodsMeta-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.
resultsAn 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.
conclusionThe 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.
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Registered trials
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