Theophylline and dyphylline pharmacokinetics in the horse.

This research investigates the pharmacokinetics, or the movement of drugs within the body, of theophylline and dyphylline in horses. Utilizing a cross-over study design, the researchers evaluated how these drugs were absorbed, distributed, metabolized, and eliminated in the horse’s body, with a focus on heart rate effects.

Methodology of the Research

• The researchers initiated the study by administering typical human dosages of theophylline and dyphylline to a single horse. This preliminary experiment allowed them to calculate appropriate dosages for the subsequent cross-over study.
• For the cross-over study, six horses were used and administered each drug. IV administration was used for both drugs to ensure complete bioavailability.

Theophylline Results

• In five of the six horses, theophylline plasma concentrations decreased in a triexponential manner after giving an IV infusion of aminophylline (a derivative of theophylline).
• The body elimination rate and half-life of theophylline were variable among the six horses, with half-lives ranging from 9.7 to 19.3 hours.
• The clearance (the volume of plasma from which a drug is completely removed per unit time) ranged between 42.3 to 69.2 ml/hr/kg.
• The distribution of the theophylline was found to take place in two phases. The initial phase was rapid (t1/2 approximately 3.5 to 4 minutes) while the second phase was slower (t1/2 approximately 1.5 to 2 hours).
• Plasma concentrations of theophylline were within the assumed effective range (10 to 20 micrograms/ml) from 15 to 40 minutes after administration.
• The volume of distribution (the theoretical volume that would be necessary to contain the total drug in the body at the same concentration that it is observed in the blood plasma) was calculated to be 1.02 L/kg.

Dyphylline Results

• The pharmacokinetics of dyphylline were best modelled by a two compartment open model in two horses and by a three-compartment open model in four horses.
• The elimination half-life of this drug ranged between 1.9 to 2.9 hours, while clearance rates were 200 to 320 ml/hr/kg.
• High enough plasma concentrations (around 50 micrograms/ml) were observed at 10 minutes after injection to elicit an effect, without causing adverse reactions.
• Concentrations above 10 micrograms/ml were observed from just after administration to about 1.5 hours later.

Effects on Heart Rate

• The researchers noted theophylline induced significant increases in heart rate.
• In contrast, dyphylline did not significantly alter the heart rate, indicating it may have less cardiac side effects compared to theophylline.

Overall, the study contributed to the understanding of how these two drugs function in the equine body. Though there were differences in pharmacokinetic parameters, both drugs were able to reach therapeutic concentrations in the horses, and therefore could potentially be used for treatment. However, due to its heart rate effects, caution may be warranted when using theophylline in horses with cardiac conditions.