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Pharmacokinetics of Codeine After Single‐and Multiple‐Oral‐Dose Administration to Normal Volunteers
Author(s) -
Guay D. R. P.,
Awni W. M.,
Halstenson C. E.,
Findlay J. W. A.,
Opsahl J. A.,
Abraham P. A.,
Jones E. C.,
Matzke Gary R.
Publication year - 1987
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1987.tb05601.x
Subject(s) - codeine , pharmacokinetics , morphine , oral administration , medicine , pharmacology , dosing , analgesic , urine , glucuronide
The pharmacokinetics of codeine, codeine glucuronide, morphine, and morphine glucuronide were assessed after single‐(60 mg) and multiple‐dose (60 mg every six hours for nine doses) oral administration of codeine sulfate to six normal volunteers. Multiple blood and urine samples were collected after administration of the single‐ and last multiple‐oral doses. Drug concentrations were analyzed using radioimmunoassay techniques. No significant alterations in codeine pharmacokinetics were noted after multiple‐dose oral administration. However, accumulation of morphine during multiple dosing was significant (AUC 24 = 102 ± 33 ng/mL/hr after single dose versus 212 ± 118 ng/mL/hr after the last multiple dose). Peak concentration and AUC 24 data for morphine glucuronide indicated that significant accumulation of this compound occurs upon multiple‐dose administration. These data indicate that morphine and morphine glucuronide serum concentrations are significantly increased during chronic oral codeine therapy and suggest that morphine, and perhaps morphine glucuronide, contribute significantly to the analgesic activity of chronic oral codeine therapy.