Intra-articular injection of morphine to the horse: establishment of an in vitro-in vivo relationship.
Abstract: In the area of parenteral depots, a strong need exists for the development of suitable in vitro drug release models that might enable establishment of in vitro-in vivo relations (IVIVRs). Objective: The objective of this study was to investigate the possibility of establishing an IVIVR between morphine disappearance from the joint cavity and in vitro release data obtained employing the rotating dialysis cell model. Methods: In vitro release experiments were conducted using the rotating dialysis cell model. For establishment of an IVIVR, data from a previous study on pharmacokinetics of intra-articular (IA) morphine in horses with lipopolysaccharide-induced synovitis were used (Lindegaard et al., (2009). Vet Anaesth Analg, 37, 186-195). Results: A rate constant of morphine disappearance from the donor phase of the in vitro model of 1.8 × 10(-2) min(-1) was calculated, independently of the different release media used. The in vivo synovial fluid disappearance rate constants were in the range of 1.0 × 10(-2)-1.7 × 10(-2) min(-1). An IVIVR (R(2) = 0.89) was established between the calculated disappearance data and the joint disappearance data. Conclusions: The results indicate that the IA fate of morphine administered in the form of a solution can be predicted from the in vitro release data obtained in the rotating dialysis cell model. Thus, this model might be a valuable tool in the establishment of IVIVRs after IA administration of drugs with similar properties.
Publication Date: 2011-03-21 PubMed ID: 21417608DOI: 10.3109/03639045.2011.559245Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study explores the potential of establishing a correlation between the in-vitro release data and in-vivo disappearance data of morphine from a horse’s joint cavity. The researchers conducted in-vitro experiments using a rotating dialysis cell model and compared the results with previous research data on the pharmacokinetics of intra-articular morphine in horses with synovitis. The findings indicate that this model could be a useful tool in predicting the behavior of similar drugs administered intra-articularly.
Objective and Methods
- The main aim of this research was to determine if there could be a relationship between the in-vitro release data and in-vivo disappearance data of morphine from a horse’s joint cavity. Such correlation is referred to as an in-vitro-in-vivo relations (IVIVRs).
- To accomplish this, the researchers used a rotating dialysis cell model to conduct in-vitro release experiments.
- For the in-vivo data, the researchers relied on a previous study that investigated the pharmacokinetics of intra-articular morphine in horses with lipopolysaccharide-induced synovitis.
Results and Conclusions
- A rate constant of morphine disappearance from the donor phase of the in-vitro model was calculated to be 1.8 × 10(-2) min(-1), regardless of the various release media used in the experiment.
- The in-vivo synovial fluid disappearance rate constants were found to be in the range of 1.0 × 10(-2)-1.7 × 10(-2) min(-1).
- Analysis of the results shows a strong correlation (R(2) = 0.89) between the calculated in-vitro release data and the in-vivo joint disappearance data.
- This correlation implies that the in-vitro release data obtained from the rotating dialysis cell model can be used to predict the fate of morphine administered intra-articularly.
- The study therefore concludes that this model can serve as a valuable tool in establishing IVIVRs for other drugs with similar properties administered intra-articularly.
Cite This Article
APA
Frost AB, Lindegaard C, Larsen F, Østergaard J, Larsen SW, Larsen C.
(2011).
Intra-articular injection of morphine to the horse: establishment of an in vitro-in vivo relationship.
Drug Dev Ind Pharm, 37(9), 1043-1048.
https://doi.org/10.3109/03639045.2011.559245 Publication
Researcher Affiliations
- Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen Ø, Denmark.
MeSH Terms
- Analgesics, Opioid / administration & dosage
- Analgesics, Opioid / pharmacokinetics
- Animals
- Horses
- Injections, Intra-Articular
- Models, Animal
- Models, Theoretical
- Morphine / administration & dosage
- Morphine / pharmacokinetics
Citations
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