ArticlePharmaceutical research2016
Pharmacokinetic/Pharmacodynamic Relationship of Gabapentin in a CFA-induced Inflammatory Hyperalgesia Rat Model.
Article in Pharmaceutical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Gabapentin: Clinical Use and Pharmacokinetics in Dogs, Cats, and Horses.Animals : an open access journal from MDPI · 2023Review
- Pharmacokinetics and pharmacodynamics of repeat dosing of gabapentin in adult horses.Journal of veterinary internal medicine · 2022Article
- A pilot study of transdermal gabapentin in cats.Journal of veterinary internal medicine · 2021Article
- Pharmacokinetic Profiles of Gabapentin after Oral and Subcutaneous Administration in Black-tailed Prairie Dogs (Journal of the American Association for Laboratory Animal Science : JAALAS · 2020Article
- Article
- The pharmacokinetics of gabapentin in cats.Journal of veterinary internal medicine · 2018Article
- Modelling the delay between pharmacokinetics and EEG effects of morphine in rats: binding kinetic versus effect compartment models.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain.Pain · 2017Article
- Population Pharmacokinetic Modelling of Morphine, Gabapentin and their Combination in the Rat.Pharmaceutical research · 2016Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeGabapentin displays non-linear drug disposition, which complicates dosing for optimal therapeutic effect. Thus, the current study was performed to elucidate the pharmacokinetic/pharmacodynamic (PKPD) relationship of gabapentin's effect on mechanical hypersensitivity in a rat model of CFA-induced inflammatory hyperalgesia.
methodsA semi-mechanistic population-based PKPD model was developed using nonlinear mixed-effects modelling, based on gabapentin plasma and brain extracellular fluid (ECF) time-concentration data and measurements of CFA-evoked mechanical hyperalgesia following administration of a range of gabapentin doses (oral and intravenous).
resultsThe plasma/brain ECF concentration-time profiles of gabapentin were adequately described with a two-compartment plasma model with saturable intestinal absorption rate (K m = 44.1 mg/kg, V max = 41.9 mg/h∙kg) and dose-dependent oral bioavailability linked to brain ECF concentration through a transit compartment. Brain ECF concentration was directly linked to a sigmoid E max function describing reversal of hyperalgesia (EC 50, plasma = 16.7 μg/mL, EC 50, brain = 3.3 μg/mL).
conclusionsThe proposed semi-mechanistic population-based PKPD model provides further knowledge into the understanding of gabapentin's non-linear pharmacokinetics and the link between plasma/brain disposition and anti-hyperalgesic effects. The model suggests that intestinal absorption is the primary source of non-linearity and that the investigated rat model provides reasonable predictions of clinically effective plasma concentrations for gabapentin.
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