Method of treating pain by administering 24 hour oral opioid formulations exhibiting rapid rate of initial rise of plasma drug level

Abstract

Patients are treated with 24-hour oral sustained release opioid formulations which, upon administration, provide an initially rapid opioid absorption such that the minimum effective analgesic concentration of the opioid is more quickly achieved. These sustained release opioid formulations include an effective amount of at least one retardant material to cause said opioid analgesic to be released at a such a rate as to provide an analgesic effect after oral administration to a human patient for at least about 24 hours, and are characterized by providing an absorption half-life from 1 to about 8 hours. A method of titrating a human patient utilizing these sustained release opioid formulations is also disclosed.

Description

[0001] The present invention relates to bioavailable sustained-release pharmaceutical formulations of analgesic drugs, in particular opioid analgesics, which provide an extended duration of effect when orally administered.[0002] It is the intent of all sustained-release preparations to provide a longer period of pharmacologic response after the administration of the drug than is ordinarily experienced after the administration of the rapid release dosage forms. Such longer periods of response provide for many inherent therapeutic benefits that are not achieved with corresponding short acting, immediate release preparations. This is especially true in the treatment of cancer patients or other patients in need of treatment for the alleviation of moderate to sever pain, where blood levels of an opioid analgesic medicament must be maintained at a therapeutically effective level to provide pain relief. Unless conventional rapid acting drug therapy is carefully administered at frequent int...

AI Technical Summary

Benefits of technology

[0013] It is accordingly an object of the present invention to provide a method for treating patients in moderate to severe pain with an orally administered pharmaceutical dosage form of an opioid analgesic that is suitable for once-a-day administration.

[0015] It is further an object of the present invention to provide an opioid analgesic dosage form which provides sustained-release of the opioid and is also capable for use in titrating a patient receiving opioid analgesic therapy.

[0017] The inventive formulations, when administered in humans, provide an initially rapid rate of rise in the plasma concentration of the opioid characterized by providing an absorption half-life from 1.5 to about 8 hours. In preferred embodiments, the inventive once-daily oral sustained release formulations provides an absorption half-life from 2 to about 4 hours.

Problems solved by technology

Unless conventional rapid acting drug therapy is carefully administered at frequent intervals to maintain effective steady state blood levels of the drug, peaks and valleys in the blood level of the active drug occur because of the rapid absorption, systemic excretion of the compound and through metabolic inactivation, thereby producing special problems in maintenance of analgesic efficacy.

However, it is generally recognized that the mere presence of an active substance in the gastrointestinal fluids does not, by itself, insure bioavailability.

Presently, however, there are no commercially available sustained-release 24-hour opioid analgesic preparations; however, experience with the 12-hour sustained release preparations have led to a general understanding in the medical community that in order to titrate a patient who is to receive opioid analgesic therapy it is necessary to use an immediate release opioid analgesic dosage form, such as a parenteral formulation, an immediate release solution or tablet, or the like.

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