Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1994 Jun;37(6):571–576. doi: 10.1111/j.1365-2125.1994.tb04306.x

Transdermal administration of morphine to healthy subjects.

D Westerling 1, P Höglund 1, S Lundin 1, P Svedman 1
PMCID: PMC1364817  PMID: 7917776

Abstract

1. Twelve healthy subjects received 10 mg morphine HCl delivered transdermally from an occlusive reservoir applied to a small area of skin, painlessly de-epithelialised by vacuum suction. On a separate occasion, 10 mg morphine HCl was given as an i.v. infusion over 20 min. 2. Venous blood samples were collected serially for 72 h and assayed for morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) by h.p.l.c. Pupil size, salivation, and central nervous effects (nausea, fatigue, headache, feeling of heaviness and dysphoria/euphoria) were also measured. 3. After transdermal application morphine was absorbed by a first-order process to produce relatively constant plasma drug concentrations over 11 h. The absolute bioavailability of transdermal morphine was 75% (65-85%; 95% CI). The plasma concentrations of both M6G and M3G were lower after transdermal administration than after i.v. infusion, and a considerable delay (of up to 1 h) was observed before the metabolites were detectable. AUC ratios for M3G and M6G relative to morphine were similar after both modes of administration. 4. Non-analgesic effects were less pronounced at the lower plasma drug and metabolite concentrations observed after transdermal delivery than after the i.v. infusion of morphine. 5. Transdermal administration of morphine warrants investigation as an alternative route of morphine delivery.

Full text

PDF
574

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bernards C. M., Hill H. F. Physical and chemical properties of drug molecules governing their diffusion through the spinal meninges. Anesthesiology. 1992 Oct;77(4):750–756. doi: 10.1097/00000542-199210000-00020. [DOI] [PubMed] [Google Scholar]
  2. Boerner U. The metabolism of morphine and heroin in man. Drug Metab Rev. 1975;4(1):39–73. doi: 10.3109/03602537508993748. [DOI] [PubMed] [Google Scholar]
  3. Borg G., Holmgren A., Lindblad I. Quantitative evaluation of chest pain. Acta Med Scand Suppl. 1981;644:43–45. doi: 10.1111/j.0954-6820.1981.tb03117.x. [DOI] [PubMed] [Google Scholar]
  4. Brunk S. F., Delle M. Morphine metabolism in man. Clin Pharmacol Ther. 1974 Jul;16(1):51–57. doi: 10.1002/cpt1974161part151. [DOI] [PubMed] [Google Scholar]
  5. Calis K. A., Kohler D. R., Corso D. M. Transdermally administered fentanyl for pain management. Clin Pharm. 1992 Jan;11(1):22–36. [PubMed] [Google Scholar]
  6. Dahlström B., Tamsen A., Paalzow L., Hartvig P. Patient-controlled analgesic therapy, Part IV: pharmacokinetics and analgesic plasma concentrations of morphine. Clin Pharmacokinet. 1982 May-Jun;7(3):266–279. doi: 10.2165/00003088-198207030-00006. [DOI] [PubMed] [Google Scholar]
  7. Heintze U., Birkhed D., Björn H. Secretion rate and buffer effect of resting and stimulated whole saliva as a function of age and sex. Swed Dent J. 1983;7(6):227–238. [PubMed] [Google Scholar]
  8. Loo J. C., Riegelman S. New method for calculating the intrinsic absorption rate of drugs. J Pharm Sci. 1968 Jun;57(6):918–928. doi: 10.1002/jps.2600570602. [DOI] [PubMed] [Google Scholar]
  9. Marks L. E., Borg G., Ljunggren G. Individual differences in perceived exertion assessed by two new methods. Percept Psychophys. 1983 Sep;34(3):280–288. doi: 10.3758/bf03202957. [DOI] [PubMed] [Google Scholar]
  10. Mather L. E. Clinical pharmacokinetics of fentanyl and its newer derivatives. Clin Pharmacokinet. 1983 Sep-Oct;8(5):422–446. doi: 10.2165/00003088-198308050-00004. [DOI] [PubMed] [Google Scholar]
  11. Miller C. D., Asbury A. J., Brown J. H. Pupillary effects of alfentanil and morphine. Br J Anaesth. 1990 Sep;65(3):415–417. doi: 10.1093/bja/65.3.415. [DOI] [PubMed] [Google Scholar]
  12. Roy S. D., Flynn G. L. Transdermal delivery of narcotic analgesics: comparative permeabilities of narcotic analgesics through human cadaver skin. Pharm Res. 1989 Oct;6(10):825–832. doi: 10.1023/a:1015944018555. [DOI] [PubMed] [Google Scholar]
  13. Sebel P. S., Barrett C. W., Kirk C. J., Heykants J. Transdermal absorption of fentanyl and sufentanil in man. Eur J Clin Pharmacol. 1987;32(5):529–531. doi: 10.1007/BF00637682. [DOI] [PubMed] [Google Scholar]
  14. Stein C. Peripheral mechanisms of opioid analgesia. Anesth Analg. 1993 Jan;76(1):182–191. doi: 10.1213/00000539-199301000-00031. [DOI] [PubMed] [Google Scholar]
  15. Svedman P., Lundin S., Svedman C. Administration of antidiuretic peptide (DDAVP) by way of suction de-epithelialised skin. Lancet. 1991 Jun 22;337(8756):1506–1509. doi: 10.1016/0140-6736(91)93197-h. [DOI] [PubMed] [Google Scholar]
  16. Säwe J., Dahlström B., Paalzow L., Rane A. Morphine kinetics in cancer patients. Clin Pharmacol Ther. 1981 Nov;30(5):629–635. doi: 10.1038/clpt.1981.214. [DOI] [PubMed] [Google Scholar]
  17. Varvel J. R., Shafer S. L., Hwang S. S., Coen P. A., Stanski D. R. Absorption characteristics of transdermally administered fentanyl. Anesthesiology. 1989 Jun;70(6):928–934. doi: 10.1097/00000542-198906000-00008. [DOI] [PubMed] [Google Scholar]
  18. Weiner D. L. NONLIN84/PCNONLIN: software for the statistical analysis of nonlinear models. Methods Find Exp Clin Pharmacol. 1986 Oct;8(10):625–628. [PubMed] [Google Scholar]
  19. Westerling D., Frigren L., Höglund P. Morphine pharmacokinetics and effects on salivation and continuous reaction times in healthy volunteers. Ther Drug Monit. 1993 Oct;15(5):364–374. doi: 10.1097/00007691-199310000-00003. [DOI] [PubMed] [Google Scholar]
  20. White I. D., Hoskin P. J., Hanks G. W., Bliss J. M. Morphine and dryness of the mouth. BMJ. 1989 May 6;298(6682):1222–1223. doi: 10.1136/bmj.298.6682.1222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Yamaoka K., Nakagawa T., Uno T. Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm. 1978 Apr;6(2):165–175. doi: 10.1007/BF01117450. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES