Abstract
The objectives of this study were to evaluate poloxamer as a slow release carrier for morphine (M) and potential tissue irritation after subcutaneous poloxamer–morphine (PM) injection in a rat model. Based on the result of a previous in vitro work, 25% poloxamer, with and without morphine, and saline were administered in 14 rats’ flanks. Blood for morphine concentrations was automatically sampled at multiple preprogrammed time points using the Culex™ unit for 48 h. Skin tissues from the injection sites were harvested and evaluated for histopathological changes. Following M or PM administration, it was determined that the half-life (t1/2) was significantly longer in the PM (5.5 ± 7.2 h) than M (0.7 ± 0.8 h) indicated a slow dissolution of poloxamer with morphine. The tmax was within 15 min and Cmax was approximately three times higher with M than with PM, reaching 716.8 (±153.7 ng/ml) of plasma morphine concentrations. There was no significant difference in total area under the curve and clearance of M versus PM. Histology inflammatory scores were similar between M, PM, and poloxamer but were significantly higher than saline control. We concluded that 25% poloxamer was capable of increasing the t1/2 of morphine, without a significant tissue irritation.
Highlights
A single administration of a slowly released analgesic that provides a sustained plasma concentration (Cp) above the minimum effective concentration is desirable to provide a longer duration of action for pain control
To the best of our knowledge, this was the first study on the use of poloxamer as a carrier for slowly release of morphine in a rat model
The t1/2 of morphine in this study was 0.94 ± 0.78 h, which was similar to that reported for dogs and cats [16], but twofold of that reported in mice [0.45 h [17]] and half of the rate in humans [2.1 h [18]]
Summary
A single administration of a slowly released analgesic that provides a sustained plasma concentration (Cp) above the minimum effective concentration is desirable to provide a longer duration of action for pain control. The advantages of such include reduction of frequent drug administration, reduced site of injection irritation, improved patient comfort and compliance. A steady state of plasma concentrations of an analgesic is routinely achieved by either constant rate infusion or via a slowly release mechanism in pain management. Constant rate infusion requires an intravenous access and sustained administration with a syringe pump over time after a loading dose.
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