Pharmacokinetics of ammonium sulfate gradient loaded liposome–encapsulated oxymorphone and hydromorphone in healthy dogs

Abstract

Objective To evaluate the pharmacokinetics, in dogs, of liposome-encapsulated oxymorphone and hydromorphone made by the ammonium sulfate gradient loading technique (ASG). Animals Four healthy purpose-bred Beagles aged 9.5 ± 3.2 months and weighing 13.4 ± 2.3 kg. Study Design Randomized cross-over design. Methods Each dog was given either 4.0 mg kg−1 of ASG-oxymorphone or 8.0 mg kg−1 of ASG-hydromorphone SC on separate occasions with a 3-month washout period. Blood was collected at baseline and at serial time points up to 1032 hours (43 days) after injection for determination of serum opioid concentrations. Serum opioid concentrations were measured with HPLC-MS and pharmacokinetic parameters were calculated using commercial software and non-compartmental methods. Results Serum concentrations of oxymorphone remained above the limit of quantification for 21 days, while those for hydromorphone remained above the limit of quantification for 29 days. Cmax for ASG-oxymorphone was 7.5 ng mL−1; Cmax for ASG-hydromorphone was 5.7 ng mL−1. Conclusions and clinical relevance Oxymorphone and hydromorphone, when encapsulated into liposomes using the ammonium sulfate gradient loading technique, result in measureable serum concentrations for between 3 to 4 weeks. This formulation may have promise in the convenient use of opioids for clinical treatment of chronically painful conditions in dogs.

A Novel Loading Method for Doxycycline Liposomes for Intracellular Drug Delivery: Characterization of In Vitro and In Vivo Release Kinetics and Efficacy in a J774A.1 Cell Line Model ofMycobacterium smegmatisInfection

“…A nonpainful injection site bulge was reported in dogs receiving a long-acting formulation, although histology was not performed (Gutierrez et al, 2014). There were no skin reactions in our previous studies with liposomal Loading Liposome Doxycycline Pharmacokinetics Efficacy 1243 at ASPET Journals on April 30, 2020 dmd.aspetjournals.org morphine, hydromorphone, and oxymorphone tested in rats, dogs, and nonhuman primates Smith et al, 2003Smith et al, , 2013. In the present study, STD-doxy-injected skin samples had a greater probability of having no lesions compared with LE-DPPC doxy-injected samples.…”

“…Liposomes have long been studied as a drug delivery system (Hunt et al, 1979). Variations in liposome composition, formation, and loading methodology may lead to strikingly different drug concentrations and release kinetics for a particular drug (Hunt et al, 1979;Omri et al, 1995;Omri and Ravaoarinoro, 1996;Sangaré et al, 1998;Krugner-Higby et al, 2003Smith et al, 2003Smith et al, , 2013Budai et al, 2009). Our laboratory has developed a novel liposome loading methodology (Heath et al, 2014).…”

A Long-Term Study of a Lipid-Buprenorphine Implant in Rats

“…Grant and coworkers demonstrated that a phospholipid-morphine liposome had prolonged activity and greater safety in mice than the free drug [ 14 ]. Lipid-based carrier strategies have been refined for the delivery of several opiates [ 15 ]. Pontani and Misra described a cholesterol-triglyceride matrix for the long-term delivery of drugs to treat chronic pain and opiate addiction [ 16 ].…”

Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in Rats

“…Grant and coworkers demonstrated that a phospholipid-morphine liposome had prolonged activity and greater safety in mice than the free drug [ 13 ]. Liposomal strategies have been refined for the delivery of several opiates [ 14 ]. Pontani and Misra described a cholesterol-triglyceride matrix for the long-term delivery of drugs to treat chronic pain and opiate addiction [ 15 ].…”