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Human Pharmacokinetic Study of Immediate‐Release (Codeine Phosphate) and Sustained‐Release (Codeine Contin) Codeine
Author(s) -
Band Christian J.,
Band Pierre R.,
Deschamps Michèle,
Besner JeanGuy,
Coldman Andrew J.
Publication year - 1994
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.1552-4604.1994.tb04008.x
Subject(s) - codeine , pharmacokinetics , cmax , bioavailability , pharmacology , chemistry , absorption (acoustics) , crossover study , medicine , placebo , morphine , physics , alternative medicine , pathology , acoustics
The authors compared, in a double‐blind, randomized, crossover study in 13 healthy adult volunteers, the single‐ and multiple‐dose pharmacokinetics, relative bioavailability, and side effects of a new oral sustained‐release formulation of codeine (SRC) containing 150 mg codeine base, with oral immediate‐release codeine phosphate (IRC). Sustained‐release codeine was given at a dose of 150 mg every 12 hours for 5 doses; IRC was given at a dose of 60 mg (2 × 30 mg) every 4 hours for the first 3 doses, and 30 mg every 4 hours thereafter for 12 doses. Plasma codeine levels were determined using a sensitive and specific high‐performance liquid chromatography method and corrected for dose administered and codeine base equivalent. Mean values for single‐dose pharmacokinetic parameters for SRC and IRC, respectively, were: C max of 217.8 and 138.8 ng/mL; T max of 2.3 and 1.1 hours; AUC 0‐inf of 1202.3 and 1262.4 ng • mL −1 • hour −1 ; and t 1/2 el of 2.6 hours for both formulations. Their respective mean steady‐state pharmacokinetic parameters were: C max of 263.8 and 222.9 ng/mL; T max of 3.2 and 1.1 hours; AUC 0–12h of 1576.4 and 1379.1 ng • mL −1 • hour −1 ; and t 1/2 el of 2.8 and 2.3 hours. These results indicate comparable bioavailability between both formulations with SRC providing delayed peak plasma levels. The sustained‐release character of SRC can be explained by a delayed absorption, which is not limiting to drug elimination. Sustained‐release codeine provides higher plasma codeine levels over a broader time interval and is expected to improve pain management.