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J Pharm Biomed Anal. 2003 Aug 8;32(4-5):867-77.

The study of codeine-gluthetimide pharmacokinetic interaction in rats.

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  • 1Department of Toxicology, University of Medicine and Pharmacy Iuliu Hatieganu, 13, Emil Isac, 3400 Cluj-Napoca, Romania. dspopa@yahoo.fr

Abstract

A high-performance liquid chromatographic (HPLC) assay with native fluorescence detection was developed for the simultaneous quantification of codeine and its two metabolites, morphine and morphine-3-glucuronide (M-3-G), in rat plasma. Solid-phase extraction was used to separate codeine and its metabolites from plasma constituents. Extraction efficiencies of codeine, morphine and M-3-G from rat plasma samples were 97, 92 and 93%, respectively. The chromatographic separation was performed using a reversed-phase C18 column and an elution gradient at ambient temperature. Using native fluorescence detection (excitation at 245 nm and emission at 345 nm), the detection limits of 50 ng/ml for morphine, 25 ng/ml for codeine and 20 ng/ml for M-3-G were obtained. The method had good precision, accuracy and linearity, and was applied to the study of glutethimide's influence on codeine metabolism in rat, following single doses of codeine-glutethimide association. The results confirmed the fact that glutethimide was responsible for a significant increase of morphine plasma levels and for their maintenance in time, concomitant with a significant decrease of M-3-G plasma levels, explained by the inhibition of morphine glucuronidation. In conclusion, glutethimide potentiates and prolongs the analgesic effect of codeine by a pharmacokinetic mechanism.

PMID:
12899973
[PubMed - indexed for MEDLINE]
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