Intra-articular injection of morphine to the horse: establishment of an in vitro-in vivo relationship.

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.