ArticleThe AAPS journal2017
Quantification of the Pharmacodynamic Interaction of Morphine and Gabapentin Using a Response Surface Approach.
Article in The AAPS journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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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
4 citing papers in PubMed.
- 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
- Clinical Management of Pain in Rodents.Comparative medicine · 2019Review
- Optimizing Dose-Finding Studies for Drug Combinations Based on Exposure-Response Models.The AAPS journal · 2019Article
- Feasibility of Exposure-Response Analyses for Clinical Dose-Ranging Studies of Drug Combinations.The AAPS journal · 2018Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The combination of morphine and gabapentin has shown to be promising for managing postoperative pain but finding the right dose for the combination has proven to be a challenge. The purpose of this study was to quantitatively characterize the pharmacodynamic interaction between the two drugs and to identify the optimal concentration-effect relationship of the combination. Information regarding plasma concentrations and von Frey withdrawal thresholds following incisional surgery on Sprague Dawley rats, after administration of morphine, gabapentin, or their combination was available from published studies. The combined pharmacodynamic effect of morphine and gabapentin was analyzed and linked to drug plasma concentrations via a response surface approach using non-linear mixed-effect modeling. Full reversal of withdrawal thresholds for the pain stimulation to presurgery values was estimated at morphine plasma concentration of 435.1 ng/mL. Co-administration of up to 40 μg/mL of gabapentin led to a reduction of the needed morphine concentration down to 307.5 ng/mL (~ 29% reduction). Combination of concentration ranges of gabapentin between 20 and 40 μg/mL with any morphine concentrations between 100 and 600 ng/mL were found to lead up to 50% increased effect relatively to the effect attained by morphine alone. This study highlights the importance of finding the right combination in multimodal analgesia and demonstrates the usefulness of the response surface approach for the study of pharmacodynamic interactions. The proposed pharmacokinetic-pharmacodynamic model may provide the basis for a rational clinical trial design with the aim to identify the optimal dose combination ratios in humans.
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