Pharmacokinetics of hydromorphone hydrochloride in healthy dogs

KuKanich, Butch; Hogan, Brynn K.; Krugner‐Higby, Lisa; Smith, Lesley

doi:10.1111/j.1467-2995.2007.00379.x

Cited by 48 publications

(63 citation statements)

References 21 publications

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“…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.…”

Section: Discussionsupporting

confidence: 91%

“…Extended-release opioid drugs have several advantages over immediate release formulations, including more stable serum concentrations, a more favorable side-effects profile, and still provide high enough concentrations in the CNS to provide analgesia to the patient (Krugner-Higby, accepted for publication; KuKanich et al 2008). Extended duration liposomal opioids suitable for use as surgical and post-surgical analgesics would be expected to have a rapid onset and a high enough peak to provide pain control during the first 24 h after surgery when pain would be expected to be most severe, but taper off rapidly enough to have minimal sedative effects later, when post-surgical pain begins to wane.…”

Section: Introductionmentioning

confidence: 99%

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

Krugner‐Higby¹,

KuKanich

Schmidt³

et al. 2011

Psychopharmacology

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Introduction This study aims to evaluate the pharmacokinetic, behavioral, and motor effects of a liposomal preparation of hydromorphone hydrochloride (LE-hydro) in rhesus monkeys. We administered either 2 mg/kg of LE-hydro (n=8) subcutaneous (s.c.) or 0.1 mg/kg of standard pharmaceutical hydromorphone HCl (hydro) preparation either intravenous (i.v.; n=4) or s.c. (n=5). Materials and methods Serial blood samples were drawn after injection and analyzed for serum hydro concentration by liquid chromatography/mass spectrometry. Following s.c. injection of 0.1 mg/kg hydro or 2 mg/kg LE-hydro, behavioral evaluations were conducted in groups of rhesus monkeys (n=10/group) in the presence of a compatible stimulus animal and motor skills were also evaluated (n=10/group). The motor skills test consisted of removing a food reward (carrot ring) from either a straight peg (simple task) or a curved peg (difficult task). Results LE-hydro (MRT0-INF = 105.9 h) demonstrated extended-release pharmacokinetics compared to hydro when administered by either i.v. (MRT0-INF =1.1 h) or s.c. (MRT0-INF =1.3 h) routes. Hydro did not affect motor performance of the simpler task, but the monkeys’ performance deteriorated on the more difficult task at 0.5 and 1 h after injection. LE-hydro had no effect on motor skills in either the simpler or more difficult task. Conclusions The results of these studies indicate that LE-hydro has a pharmacokinetic and behavioral side effects profile consistent with an analgesic that could be tested for surgical use in animals. Our studies also expand the use of rhesus monkeys as a translational behavioral pharmacodynamics model for testing extended-release opioid medication.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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

Krugner‐Higby¹,

KuKanich

Schmidt³

et al. 2011

Psychopharmacology

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“…The use of opioids in the management of both acute and chronic pain is therefore a useful alternative. Opioids are considered the most reliable and effective analgesic, although they can produce reversible behavioral [8] and physiological [9] side effects in dogs.…”

Section: Introductionmentioning

confidence: 99%

Subcutaneous Administration of Tramadol after Elective Surgery Is as Effective as Intravenous Administration in Relieving Acute Pain and Inflammation in Dogs

Salisu

Hashim

Goh

et al. 2012

The Scientific World Journal

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Subcutaneous (SC) administration of tramadol was compared with intravenous (IV) administration to evaluate analgesia following canine ovariohysterectomy (OHE). Healthy female dogs (n = 12) between 1 and 3 years of age (1.95 ± 0.65 years), weighing between 10.5 and 17.1 kg (13.12 ± 1.95 kg), were used. Pain was assessed at baseline before surgery and then hourly for 8 hr after surgery. Tramadol was administered both SC and IV at a dose of 3 mg/kg and provided significant postoperative analgesia, as indicated by analgesiometry, β-endorphin levels, and interleukin 6 (IL-6) levels. The respiratory rates and rectal temperatures remained normal and were not significantly different between or within the groups. A significant increase in heart rate was observed at 4 hr for dogs in both groups relative to the baseline, but there was no significant difference in heart rates between the groups at any time point. A significant decrease in mechanical pain threshold was observed within each group after surgery, but both groups responded similarly, suggesting that SC administration of tramadol is as effective as IV administration. Increased serum levels of both IL-6 and β-endorphin 3 hr postoperatively further indicate that both routes of administration achieve similar pain control. Thus, the relative analgesic efficacy of SC tramadol is comparable to that of IV administration and can be used to achieve similar effects for postsurgical pain management in dogs undergoing OHE.

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“…Some dogs also vomited, defecated, salivated, panted, and/or vocalized after treatment. In this study we did not record sedation or incidence of other side effects, such as vomition, but this information has been published by our laboratory in pharmacokinetic studies of hydromorphone HCl and LEH in beagle dogs of similar age and weight (Kukanich et al, 2008a; Smith et al, 2008). In this study, one dog in the placebo group panted from baseline to 1 h after treatment, two dogs in the LEH group panted from 5 min to 2 h after treatment, and 3 dogs in the hydromorphone HCl group panted from 15 min to 1 h after treatment.…”

Section: Resultsmentioning

confidence: 99%

“…Of the available analgesics, opioids have been shown to offer the most reliable, effective analgesia for acute pain management and perioperative analgesia (Pascoe, 2000). In dogs, behavioral side effects of opioids, particularly hydromorphone, include panting, vocalization, salivation, nausea, vomition, defecation, and sedation or hyperactivity (Kukanich et al, 2008a). Physiologic side effects of opioids in dogs may include CNS depression, respiratory depression, bradycardia, usually accompanied with little to no change in cardiac output, ileus, and urinary retention (Wagner, 2002).…”

Section: Introductionmentioning

confidence: 99%

A comparison of the effects of hydromorphone HCl and a novel extended release hydromorphone on arterial blood gas values in conscious healthy dogs

Wunsch¹,

Schmidt²,

Krugner‐Higby³

et al. 2010

Research in Veterinary Science

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The purpose of this study was to evaluate arterial blood gases in dogs that were given hydromorphone or extended release liposome-encapsulated hydromorphone (LEH). Dogs were randomly administered LEH, n = 6, (2.0 mg kg−1), hydromorphone, n = 6, (0.2 mg kg−1) or a placebo of blank liposomes, n = 3, subcutaneously on separate occasions. Arterial blood samples were drawn at serial time points over a 6-h time period for blood gas analysis. There was no change from baseline values in PaCO2, PaO2, (HCO3−), pH, and SBEc in the dogs that received the placebo. Administration of hydromorphone resulted in significant increases in PaCO2 (maximum (mean + SD] 44.4 + 1.1 mm of Hg) and significant decreases in PaCO2 (minimum (mean + SD) 82.4 + 4.7 mm of Hg) and pH (minimum (mean + SD) 7.31 + 0.01) compared with baseline. Administration of LEH resulted in significant increases in PaCO2 (maximum (mean + SD) 44.6 + 0.9 mm of Hg) and significant decreases in PaO2 (minimum (mean + SD) 84.8 + 2.6 mm of Hg) and pH (minimum (mean + SD) 7.34 + 0.02) compared with baseline. There was no significant difference between these two groups at any time point. The changes observed in PaCO2, PaO2, and pH, however, were within clinically acceptable limits for healthy dogs. LEH was determined to cause moderate changes in arterial blood gas values similar to those caused by hydromorphone.

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Pharmacokinetics of hydromorphone hydrochloride in healthy dogs

Cited by 48 publications

References 21 publications

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

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

Subcutaneous Administration of Tramadol after Elective Surgery Is as Effective as Intravenous Administration in Relieving Acute Pain and Inflammation in Dogs

A comparison of the effects of hydromorphone HCl and a novel extended release hydromorphone on arterial blood gas values in conscious healthy dogs

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