Pharmacokinetics of codeine after single- and multiple-oral-dose administration to normal volunteers.

Abstract:

: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 (AUC24 = 102 +/- 33 ng/mL/hr after single dose versus 212 +/- 118 ng/mL/hr after the last multiple dose). Peak concentration and AUC24 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.

journal_name

J Clin Pharmacol

authors

Guay DR,Awni WM,Halstenson CE,Findlay JW,Opsahl JA,Abraham PA,Jones EC,Matzke GR

doi

10.1002/j.1552-4604.1987.tb05601.x

subject

Has Abstract

pub_date

1987-12-01 00:00:00

pages

983-7

issue

12

eissn

0091-2700

issn

1552-4604

journal_volume

27

pub_type

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