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Rectal administration of nicomorphine in patients improves biological availability of morphine and its glucuronide conjugates

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Abstract

The pharmacokinetics of 30 mg nicomorphine after rectal administration with a suppository are described in 8 patients under combined general and epidural anaesthesia. No nicomorphine or 6-mononicotinoylmorphine could be detected in the serum. Morphine appeared almost instantaneously with a lag-time of 8 min and had a final elimination half-life of 1.48±0.48 h. Morphine was metabolized to morphine-3-glucuronide and morphine-6-glucuronide. These glucuronide conjugates appeared after a lag-time of 12 min and the half-life of these two glucuronide conjugates was similar: about 2.8 h (P>0.8). The glucuronide conjugate of 6-mononicotinoylmorphine was not detected. In the urine only morphine and its glucuronides were found. The renal clearance value for morphine was 162 m·min−1 and for the glucuronides 81 ml·min−1. This study shows that administration of a suppository with 30 mg nicomorphine gives an excellent absolute bioavailability of morphine and its metabolites of 88%. The lipid-soluble prodrug nicomorphine is quickly absorbed and immediately hydrolysed to morphine.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, Academic Hospital Nijmegen Sint Radboud, Geert Grooteplein Zuid 8, 6525, GA Nijmegen, the Netherlands

    P. M. Koopman-Kimenai & T. B. Vree

  2. Institute of Anaesthesiology, Academic Hospital Nijmegen Sint Radboud, the Netherlands

    T. B. Vree, L. H. D. J. Booij & R. Dirksen

Authors
  1. P. M. Koopman-Kimenai
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  2. T. B. Vree
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  3. L. H. D. J. Booij
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  4. R. Dirksen
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Koopman-Kimenai, P.M., Vree, T.B., Booij, L.H.D.J. et al. Rectal administration of nicomorphine in patients improves biological availability of morphine and its glucuronide conjugates. Pharm World Sci 16, 348–353 (1994). https://doi.org/10.1007/BF02178565

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