On the Forefront: Extended-release liposomal opioids for treating pain in dogs - Veterinary Medicine
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On the Forefront: Extended-release liposomal opioids for treating pain in dogs


VETERINARY MEDICINE



Figure 2. In vitro characteristics of DPPC-cholesterol liposomal oxymorphone and hydromorphone drug release over time.
We have since developed liposomal oxymorphone and hydromorphone with a more stable liposomal membrane made from both cholesterol and dipalmitoylphosphatidylcholine (DPPC) that has a release time of over 13 days (Figure 2). Both egg phosphatidylcholine and DPPC-cholesterol liposomal opioid formulations not only have predictable release times but also offer potential for a convenient dosing interval of once every one or two weeks; a subcutaneous route of administration by the veterinarian, making access by the pet or by human caretakers impossible; and reduced side effects because of the slow, steady release of drug without a bolus effect.

Since developing liposomal oxymorphone and hydromorphone in the laboratory, we have tested their efficacy and safety in rats, mice, dogs, and, recently, nonhuman primates. Much of this data is preliminary, but we have recently gained funding from the Morris Animal Foundation and from the National Institutes of Health that allows us to investigate the potential clinical application of these drug formulations.

Thus far, we have shown that one subcutaneous injection of liposomal oxymorphone provides effective analgesia for seven days in a rat model of neuropathic pain9 and in a rat and mouse model of postoperative visceral pain.10,11 We have also shown that a single dose of liposomal oxymorphone provided therapeutic serum concentrations of drug for three days in healthy dogs.12 Work with liposomal hydromorphone in rats has recently been completed (Smith LJ, et al, School of Veterinary Medicine, University of Wisconsin, Madison, WI: Unpublished data, 2005). These studies were all performed with egg phosphatidylcholine liposomes; studies with cholesterol-containing DPPC liposome-encapsulated oxymorphone or hydromorphone in animals will be conducted to evaluate the duration of therapeutic serum concentrations.

Currently, our laboratory is focusing on pharmacokinetic studies in dogs, rats, and nonhuman primates to better describe the biologic behavior of liposomal oxymorphone and hydromorphone. We are also testing analgesic thresholds after administering these drugs to healthy, nonpainful animals. We plan to study the side effects of these drug formulations by evaluating mental status, heart rate, and arterial blood gases.

The next steps

Liposomal oxymorphone and hydromorphone are not yet commercially available. We anticipate that in the next several years we will be testing the analgesic efficacy of liposomal opioids in client-owned dogs with postoperative pain and dogs with chronically painful conditions such as osteoarthritis or cancer. In the future, we may investigate the effects of liposomal opioids given epidurally.

Much potential exists in the clinical application of liposomal opioids for many veterinary and laboratory animal species. The extended dosing interval and reduced potential for access make them ideal for use in large laboratory animal colonies.

Questions concerning current or future studies with liposomal oxymorphone or liposomal hydromorphone can be directed to Dr. Lesley J. Smith at the Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive, Madison WI 53706; or call (608) 263-9808, fax (608) 263-7930, or e-mail

REFERENCES

1. Hellyer PW. Treatment of pain in dogs and cats. J Am Vet Med Assoc 2002;221:212-215.

2. Lascelles BDX, Main DCJ. Surgical trauma and chronically painful conditions–within our comfort level but beyond theirs? J Am Vet Med Assoc 2002;221:215-222.

3. Kyles AE, Ruslander D. Chronic pain: osteoarthritis and cancer. Semin Vet Med Surg (Small Animal) 1997;12:122-132.

4. Haskins SC. Advantages and guidelines for using agonist opioid analgesics. Vet Clin North Am Small Anim Pract 1992;22:360-362.


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