Pharmacokinetics of two novel rectal controlled-release morphine formulations
| Autor: | Thinnayam N. Krishnamurthy, June A. Anslow, Andrew C. Darke, Najib Babul |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Adult
Male Morphine business.industry Cmax Biological Availability Suppository Pharmacology Crossover study Dosage form Bioavailability Route of administration Anesthesiology and Pain Medicine Pharmacokinetics Administration Rectal Anesthesia Rectal administration Delayed-Action Preparations Medicine Humans Neurology (clinical) business General Nursing |
| Zdroj: | Journal of pain and symptom management. 7(7) |
| ISSN: | 0885-3924 |
| Popis: | Administration of morphine by the oral route is not possible in cancer patients who are unable to swallow or are intolerant of oral morphine. Thus, there is a need for reliable alternate routes of drug administration. We compared the bioavailability of two prototype 30-mg morphine sulfate controlled-release suppository formulations (high and low viscosity) with 30-mg oral controlled-release morphine sulfate tablets in a 14-subject single-dose randomized, three-way crossover study. Venous blood samples were obtained immediately prior to and for 24 hr following each dose. Morphine concentrations were determined by radioimmunoassay. Compared with oral controlled-release morphine, the high- and low-viscosity suppository formulations had significantly greater bioavailability (AUC0-24 72.7 +/- 13.2 for the oral preparation versus 98.6 +/- 35.7 and 105.8 +/- 37.3 ng.hr/mL for the suppositories, respectively, P < 0.05), later peak concentration (tmax 2.3 +/- 0.8 versus 3.1 +/- 2.3 and 5.0 +/- 1.5 hr, respectively, P < 0.05), and longer half-value duration (4.3 +/- 1.6 versus 10.4 +/- 5.5 and 9.5 +/- 4.3 hr, respectively, P < 0.05). Peak concentration for the high-viscosity suppository formulation (Cmax 7.75 +/- 2.66 ng/mL) was significantly lower than the low-viscosity suppository (Cmax 9.23 +/- 2.85 ng/mL) and the oral tablet (Cmax 10.4 +/- 2.78 ng/mL) formulations (P < 0.05). The increased bioavailability observed with the two controlled-release suppositories may be the result of partial avoidance of hepatic biotransformation with rectal administration. |
| Databáze: | OpenAIRE |
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