Pharmacokinetic disposition of an immediate-release aminophylline and a sustained-release theophylline formulation in the horse.

The research study analyzes the pharmacokinetic behavior of theophylline, a drug used to treat respiratory diseases in horses, when administered through different formulations: intravenous aminophylline, immediate-release aminophylline tablets, and sustained-release theophylline tablets. The focus is to compare how quickly these different formulations are absorbed, distributed, metabolized, and excreted.

Experimental Approach

• The experiment involved six healthy, adult horses that were given aminophylline intravenously and in the form of immediate-release tablets, as well as theophylline in sustained-release tablet form.
• The doses of aminophylline (both intravenously and in tablet form) were given at an equivalent of 9.94 mg/kg of theophylline, while the sustained-release theophylline tablet was administered at 20 mg/kg.
• The researchers obtained plasma samples from the horses after the administration to determine theophylline levels. The analysis was conducted using a high-performance liquid chromatographic method.

Results and Analysis

• The elimination rate constant (lambda z), apparent volume of distribution (Vz), and clearance (Cl) obtained from the intravenous administration were determined. These metrics help in understanding the behavior of the drug in the body.
• The researchers also calculated the mean residence time, which indicates the average time the drug stays in the body. It was found that the mean residence time for the immediate-release aminophylline was significantly lower than the sustained-release theophylline.
• The immediate-release aminophylline tablets resulted in quicker absorption of theophylline, with peak plasma concentrations achieved approximately 1.6 hours after administration. Sustained-release theophylline tablets, on the other hand, took around 7.3 hours to reach peak plasma concentrations, indicating slower absorption.
• In terms of bioavailability (the degree to which a drug becomes available to the target tissue after administration), the immediate-release formulation showed 87% bioavailability and the sustained-release formulation showed 97% bioavailability. This means both formulations have high bioavailability, which is highly favorable, with the sustained-release formulation being slightly more efficient.

Conclusions

• Based on the principle of superposition and the drug’s pharmacokinetic profile, the researchers predicted that a loading dose (initial high dose used to quickly get the drug into the bloodstream) of 20 mg/kg of sustained-release theophylline, followed by maintenance doses of 15 mg/kg every 24 hours, would maintain theophylline plasma concentrations between 6 and 17 micrograms/ml.