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

Abstract

Buprenorphine is absorbed following sublingual administration, which would be a low‐stress delivery route in foals. However, the pharmacokinetics/pharmacodynamics are not described in foals. Six healthy foals <21 days of age participated in a blinded, randomized, 3‐period, 5‐sequence, 3‐treatment crossover prospective study. Foals received 0.01–0.02 mg/kg buprenorphine administered SL or IV with an equivalent volume of saline administered by the opposite route. Blood was collected from the cephalic vein for pharmacokinetic analysis. Physiologic parameters (HR, RR, body temperature, GI sounds), locomotion (pedometer), and behavioral data (activity level, nursing time, response to humans) were recorded. Plasma concentration of buprenorphine exceeded a presumed analgesic level (0.6 ng/ml) in five foals in the IV group and one in the SL group but only for a very brief time. Pharmacokinetic analysis following IV administration demonstrated a short elimination half‐life (t1/2β 1.95 ± 0.7 hr), large volume of distribution (6.46 ± 1.54 L/kg), and a high total clearance (55.83 ± 23.75 ml/kg/min), which differs from adult horses. Following SL administration, maximum concentrations reached were 0.61 ± 0.11 ng/ml and bioavailability was 25.1% ± 10.9%. In both groups, there were minor statistical differences in HR, RR, body temperature, locomotion, and time spent nursing. However, these differences were clinically insignificant in this single dose study, and excitement, sedation, or colic did not occur.

Evaluation of physical variables, thermal nociceptive threshold testing and pharmacokinetics during placement of transdermal buprenorphine matrix-type patch in healthy adult horses

“…The primary metabolite of buprenorphine is norbuprenorphine, which was undetectable following transdermal administration in the study. This analysis was in accordance with previous studies where norbuprenorphine was unmeasurable following either intravenous or sublingual route ( 38 , 40 , 42 ). Considering norbuprenorphine has only 25% of the intrinsic analgesic activity of buprenorphine and a low permeability into the brain, it may have minimal clinical significance ( 45 ).…”

“…Previous exploratory studies with buprenorphine in horses utilized average doses of 5–10 µg/kg via intravenous ( 18 , 20 , 21 , 33 – 41 ), intramuscular ( 23 , 24 , 38 , 42 ) and sub-lingual ( 40 , 42 , 43 ) routes. A common observation in most of these studies irrespective of the route used was its potential for inducing excitement, increasing spontaneous locomotory activity, decreasing gut sounds and elevating HR in healthy pain-free horses.…”

BEVA primary care clinical guidelines: Analgesia

“…Bioavailability of buprenorphine from the sublingual route has been investigated in two studies; one study documented good absorption when plasma concentrations were measured in samples from the jugular vein, but the study also demonstrated a significantly higher concentration in blood obtained from the jugular vein than blood obtained from the lateral thoracic vein, although pharmacokinetics were not determined from these samples . A second study, in foals, demonstrated only 25% bioavailability when plasma concentrations were measured in samples taken from the cephalic vein and the sublingual dose tested (0.02 mg/kg) failed to achieve plasma concentrations associated with analgesia in experimental models . The dose used in the case report described above was one‐third of this dose (0.006 mg/kg).…”

Plasma concentrations of buprenorphine administered via matrix-type transdermal patches applied at three different anatomical locations in healthy adult horses

“…Previous exploratory studies with buprenorphine in horses utilized average doses of 5–10 µg/kg via intravenous ( 18 , 20 , 21 , 40 , 42 – 48 ), intramuscular ( 23 , 24 , 39 , 49 ), and sublingual ( 40 , 42 , 50 ) routes. A common observation in most of these studies irrespective of the route used was its potential for inducing excitement, increasing spontaneous locomotory activity, decreasing gut sounds, and elevating HR in healthy pain-free horses.…”