Pharmacokinetics and physiological effects of intravenous hydromorphone in conscious dogs

Abstract

This study evaluated the pharmacokinetics, the sedative and anti-nociceptive effects of intravenous hydromorphone in dogs. Five adult dogs were administered hydromorphone (0.1 mg/kg and 0.2 mg/kg) and morphine (0.5 mg/kg and 1 mg/kg) at weekly intervals. Blood samples were drawn before and at 1, 2, 5, 15, 30, 60 and 120 min after drug administration. Plasma hydromorphone only was measured by high pressure liquid chromatography (HPLC) with electrochemical detection and pharmacokinetic parameters calculated. Anti-nociceptive and sedation scores were submitted to Kruskal-Wallis one-way anova on ranks and post-hoc Bonferroni test with 5% significance level. The data fitted a two-compartment model with a fast distribution (<1 min for both doses) and slower elimination rate. Mean elimination half-life was 80 +/- 52.7 and 57.7 +/- 30.4 min for the high and low dose, respectively. The apparent mean volumes of distribution at steady-state were 7.2 +/- 3 and 4.5 +/- 2.4 L/kg, while the clearance was 74.7 +/- 19 and 68.1 +/- 20 mL/kg/min for the high and low doses, respectively. Compared to saline, hydromorphone and morphine produced significant anti-nociception and sedation of similar magnitude for 120 min. In conclusion, intravenous hydromorphone has a large volume of distribution, and high clearance rate that exceeds hepatic blood flow. In dogs, it produced mechanical anti-nociception and sedation of a magnitude similar to morphine.

Pharmacokinetics and behavioral effects of liposomal hydromorphone suitable for perioperative use in rhesus macaques

“…The pharmacokinetics of hydro in rhesus monkeys determined by LC/MS analysis in this study agrees well with previous studies in dogs (Guedes et al 2008; KuKanich et al 2008) and with previous studies in rhesus monkeys using C-11 radiolabeled hydromorphone (Hartvig et al 1989). The half-life of 0.1 mg/kg hydro administered i.v.…”

“…in dogs is consistent with 60 min of analgesic efficacy, based on the assumption that plasma/serum drug concentrations must be at least 4 ng/mL (Coda et al 1997; KuKanich et al 2008; Reidenberg et al 1988). However, this same dose produced 120 min of analgesia in a dog analgesiometry model, so it is possible that serum drug concentrations lower than 4 ng/mL may be clinically useful in dogs (Guedes et al 2008). A lag from the decrease in serum drug concentrations to loss of effect (hysteresis) may also occur with hydromorphone in dogs, similar to that of morphine in dogs (KuKanich et al 2007) which may explain the duration of effect lasting longer than serum drug concentrations.…”

Effect of cold compress application on tissue temperature in healthy dogs

“…Adrenoceptor agonist opioids such as hydromorphone induce a thermoregulatory response that results in hypothermia in dogs. 31,32 Results of the study reported here, with a decrease in temperature at the measured tissue depths in the control group, were supportive of a hypothermic response. The use of µ-adrenoceptor agonists has a strong association with hypothermia in dogs; however, such opioids are frequently used during the same time period that cold compress treatment would be applied in small animal surgical patients; thus, this methodology does resemble a typical clinical scenario.…”

“…15,25,30 Administration of hydromorphone to dogs decreases body temperature. 31,32 Specific opioid receptors are thought to induce different thermic responses. Adrenoceptor agonist opioids such as hydromorphone induce a thermoregulatory response that results in hypothermia in dogs.…”

Pharmacokinetics of hydrocodone and hydromorphone after oral hydrocodone in healthy Greyhound dogs

“…Previous studies of 0.2 mg/kg IV hydromorphone suggest antinociceptive effects for 4 h using an electrical stimulus (Wegner et al, 2008). Pharmacokinetic studies suggest plasma hydromorphone concentrations are approximately 1.6 ng/mL at 4 h after dosing (Guedes et al, 2008). The plasma concentrations of hydromorphone after oral hydrocodone exceeded 1.6 ng/mL through 8 h in this study.…”