Pharmacokinetics and physiologic/behavioral effects of buprenorphine administered sublingually and intravenously to neonatal foals.

The study aims to explore whether buprenorphine, a painkiller, is effectively absorbed when administered sublingually (under the tongue) in neonatal foals (young horses less than 21 days old). It further investigates the drug’s physiological and behavioral impact.

Study Design and Methods

• The research involved six healthy foals under 21 days of age. It was designed as a blinded, randomized, 3-period, 5-sequence, 3-treatment crossover prospective study, meaning the foals received different treatments in a random order, and neither the individuals administering the treatments nor the foals knew which was being administered.
• The foals received 0.01-0.02 mg/kg of buprenorphine administered either sublingually (SL) or intravenously (IV) with an equivalent volume of saline administered by the opposite route, i.e., if buprenorphine was given intravenously, the saline was given sublingually and vice versa.
• The researchers regularly collected blood from the foals for pharmacokinetic analysis, to track how the drug was absorbed, distributed, metabolized, and excreted.
• They also recorded various physiological parameters (heart rate – HR, respiratory rate – RR, body temperature, gastrointestinal sounds), movement (using a pedometer), and behavioral data (activity level, nursing time, response to humans).

Results and Findings

• Pharmacokinetic analysis following IV administration showed a short elimination half-life (1.95 ± 0.7 hours), a large volume of distribution (6.46 ± 1.54 L/kg), and a high total clearance (55.83 ± 23.75 ml/kg/min), indicating that buprenorphine rapidly spread throughout the body and was quickly eliminated from it. This is different from what is usually observed in adult horses.
• Following SL administration, maximum concentrations reached were 0.61 ± 0.11 ng/ml and bioavailability was 25.1% ± 10.9%. Here, bioavailability refers to the proportion of the drug that reaches circulation and can potentially have an effect. A lower bioavailability suggests that a significant portion of the drug was not absorbed effectively.
• Plasma concentration of buprenorphine exceeded a presumed painkilling level (0.6 ng/ml) in five foals in the IV group and one in the SL group but only for a very short time.
• In both groups, there were minor statistical differences in HR, RR, body temperature, locomotion, and time spent nursing. However, these differences were considered clinically insignificant in this single dose study.
• Importantly, the foals did not exhibit signs of excitement, sedation, or colic, implying that the drug did not cause immediate or significant side effects.

Conclusion

• The study suggests that buprenorphine is absorbed following both sublingual and intravenous administration in neonatal foals.
• However, buprenorphine’s pharmacokinetics following SL administration in neonatal foals were different from those observed in adult horses, with a lower bioavailability and shorter duration of effective drug levels in blood.
• Despite this, the minor changes observed in physiological and behavioural parameters suggest that a single sublingual dose may have minimal negative effects in this population.