Pharmacokinetics of subcutaneous ketamine administration via the Omnipod® system in dogs.

Ketamine is an injectable anesthetic agent with analgesic and antidepressant effects that can prevent maladaptive pain. Ketamine is metabolized by the liver into norketamine, an active metabolite. Prior rodent studies have suggested that norketamine is thought to contribute up to 30% of ketamine's analgesic effect. Ketamine is usually administered as an intravenous (IV) bolus injection or continuous rate infusion (CRI) but can be administered subcutaneously (SC) and intramuscularly (IM). The Omnipod® is a wireless, subcutaneous insulin delivery device that adheres to the skin and delivers insulin as an SC CRI. The Omnipod® was used in dogs for postoperative administration of ketamine as a 1 mg/kg infusion bolus (IB) over 1 hour (h). Pharmacokinetics (PK) showed plasma ketamine concentrations between 42 and 326.1 ng/mL. The median peak plasma concentration was 79.5 (41.9-326.1) ng/mL with a Tmax of 60 (30-75) min. After the same infusion bolus, the corresponding norketamine PK showed plasma drug concentrations between 22.0 and 64.8 ng/mL. The median peak plasma concentration was 43.0 (26.1-71.8) ng/mL with a median Tmax of 75 min. The median peak ketamine plasma concentration exceeded 100 ng/mL in dogs for less than 1 h post infusion. The Omnipod® system successfully delivered subcutaneous ketamine to dogs in the postoperatively.

Novel subcutaneous cytarabine infusion with the Omnipod system in dogs with meningoencephalomyelitis of unknown etiology.

OBJECTIVE: To investigate the feasibility and pharmacokinetics of cytarabine delivery as a subcutaneous continuous-rate infusion with the Omnipod system. ANIMALS: 6 client-owned dogs diagnosed with meningoencephalomyelitis of unknown etiology were enrolled through the North Carolina State University Veterinary Hospital. PROCEDURES: Cytarabine was delivered at a rate of 50 mg/m2/hour as an SC continuous-rate infusion over 8 hours using the Omnipod system. Plasma samples were collected at 0, 4, 6, 8, 10, 12, and 14 hours after initiation of the infusion. Plasma cytarabine concentrations were measured by high-pressure liquid chromatography. A nonlinear mixed-effects approach generated population pharmacokinetic parameter estimates. RESULTS: The mean peak plasma concentration (Cmax) was 7,510 ng/mL (range, 5,040 to 9,690 ng/mL; SD, 1,912.41 ng/mL), average time to Cmax was 7 hours (range, 4 to 8 hours; SD, 1.67 hours), terminal half-life was 1.13 hours (SD, 0.29 hour), and the mean area under the curve was 52,996.82 hours X µg/mL (range, 35,963.67 to 71,848.37 hours X µg/mL; SD, 12,960.90 hours X µg/mL). Cmax concentrations for all dogs were more than 1,000 ng/mL (1.0 µg/mL) at the 4-, 6-, 8-, and 10-hour time points. CLINICAL RELEVANCE: An SC continuous-rate infusion of cytarabine via the Omnipod system is feasible in dogs and was able to achieve a steady-state concentration of more than 1 µg/mL 4 to 10 hours postinitiation of cytarabine and a Cmax of 7,510 ng/mL (range, 5,040 to 9,690 ng/mL; SD, 1,912.41 ng/mL). These are comparable to values reported previously with IV continuous-rate infusion administration in healthy research Beagles and dogs with meningoencephalomyelitis of unknown etiology.

The bioavailability of cytarabine in dogs with meningoencephalitis of unknown etiology through iontophoresis and rectal delivery.

Background: Cytarabine (CA) is used to treat dogs with meningoencephalitis of unknown etiology (MUE) by subcutaneous or intravenous administration. Aim: The objective was to investigate transdermal iontophoresis and rectal administration as alternative routes of CA delivery. Methods: Two client-owned dogs with MUE were studied. The ActivaPatch® IONTOGO™ 12.0 iontophoresis drug delivery system delivered 200 mg/m2 CA transdermally. Blood samples were collected by sparse sampling technique after initiation of the device. At another visit, 100 mg/m2 CA was administered rectally. Blood samples were collected by sparse sampling technique after administration. Plasma CA concentrations were measured by high-pressure liquid chromatography. Results: The concentration of plasma CA after transdermal and rectal administration was below the limits of quantification (0.1 µg/ml) in all samples suggesting inadequate bioavailability with transdermal and rectal administration. Conclusion: Transdermal and rectal CA administration are not reasonable alternative routes of delivery.