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The Use of Pharmacoscintigraphy to Elucidate Food Effects Observed with a Novel Protease Inhibitor (Saquinavir)

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Abstract

Purpose. To evaluate mechanistically the effect of food on the absorption and gastrointestinal transit of the protease inhibitor saquinavir.

Methods. Pharmacoscintigraphic investigation in eight healthy volunteers.

Results. Gastric emptying occurred rapidly in the fasted state with some capsules leaving the stomach prior to disintegration. Unmeasur-able plasma concentrations were observed in several subjects when dosed under fasted conditions. Following post-prandial administration the radioactive marker became re-distributed within the stomach contents and consequently slower gastric emptying resulted. Plasma concentrations under fed conditions were measurable up to 12 hrs after administration in seven of the eight subjects. Six of the eight plasma profiles showed secondary peaks at c. 4 hours post-dose; two of which coincided with the gastrocolonic response following ingestion of lunch.

Conclusions. Bioavailability of saquinavir is significantly improved in the presence of food. Emptying of intact capsules in the fasted state may further reduce bioavailability. In the fed state, capsules disintegrate rapidly and gastric emptying is prolonged which may improve exposure of the drug to target absorption sites. Saquinavir may be absorbed from the colon. Second peaks in the absorption profile can only be attributed to gastrocolonic response following ingestion of a meal in some cases. Increased absorption is more likely to be due to an increase in dissolved drug being available for absorption due to general increased motility and secretion stimulated by ingestion of a meal.

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REFERENCES

  1. R. A. Kramer, M. D. Schaber, A. M. Skala et al. Science 231:1580 (1986).

    PubMed  Google Scholar 

  2. J. C. Craig, C. Greif, J. S. Mills et al. Antivir. Chem. Chemother. 2:188–186 (1991).

    Google Scholar 

  3. R. Pauwels, K. Andries, J. Desmyter et al. Nature 343:470 (1996).

    Article  Google Scholar 

  4. G. Moyle. Exp. Opin. Invest. Drugs 5:155–167 (1996).

    Google Scholar 

  5. V. S. Kitchen, C. Skinner, K. Ariyoshi et al. Lancet 345:952–955 (1995).

    Article  PubMed  Google Scholar 

  6. S. S. Davis, J. G. Hardy, S. P. Newman, and I. R. Wilding. Eur. J. Nucl. Med. 19:971–986 (1992).

    PubMed  Google Scholar 

  7. J. N. Hunt and I. MacDonald. J. Physiol. 126:459–474 (1954).

    PubMed  Google Scholar 

  8. I. R. Wilding, S. S. Davis, K. P. Steed, R. A. Sparrow, J. Westrup, and J. M. Hempenstall. Int. J. Pharm. 101:263–268 (1994).

    Google Scholar 

  9. C. F. Code and J. A. Martlett. J. Physiol. 246:289–309 (1975).

    PubMed  Google Scholar 

  10. S. S. Davis, J. G. Hardy, and J. W. Fara. Gut. 27:886–892 (1986).

    PubMed  Google Scholar 

  11. J. M. C. Price, S. S. Davis, R. A. Sparrow, and I. R. Wilding. Pharm. Res. 10:722–726 (1993).

    PubMed  Google Scholar 

  12. J. N. Hunt and D. F. Stubbs. J. Physiol. 245:209–225 (1975).

    PubMed  Google Scholar 

  13. G. Moyle and B. Gazzard. Drugs 51(5):701–712 (1996).

    PubMed  Google Scholar 

  14. J. A. Ganley, J. McEwan, R. T. Calvert, and M. C. J. Barker. J. Pharm. Pharmacol. 36:734–739 (1984).

    PubMed  Google Scholar 

  15. J. B. Dressman, P. Bass, W. A. Ritschel, D. R. Friend, A. Rubinstein, and E. Ziv J. Pharm. Sci. 82(9):857–872 (1993).

    PubMed  Google Scholar 

  16. L. Williams, D. P. Hill, J. A. Davis, and D. T. Lowenthal. European Journal of Drug Metabolism and Pharmacokinetics 21(3):201–211 (1996).

    PubMed  Google Scholar 

  17. M. G. Sarr, K. A. Kelly, and S. F. Philips. Am. J. Physiol. 239:G167–172 (1980).

    PubMed  Google Scholar 

  18. N. F. LaRusso, M. G. Korman, N. E. Hoffman, and A. F. Hoffman. New England Journal of Medicine 291:689–692 (1974).

    PubMed  Google Scholar 

  19. R. Aldini, A. Roda, M. Montagnani, and E. Roda. Italian Journal of Gastroenterology 27(3):141–144 (1995).

    PubMed  Google Scholar 

  20. Anonymous. Scrip. 2216:28 (21 March 1997).

  21. J. M. Schapiro, M. A. Winters, M. J. Kozal et al. 35th Interscience Conference on Antimicrobial agents and Chemotherapy: 1995 Sep 17–20; San Francisco.

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Authors and Affiliations

  1. Pharmaceutical Profiles Limited, 2 Faraday Building, Highfields Science Park, Nottingham, NG7 2QP, UK

    C. J. Kenyon & I. R. Wilding

  2. Roche Products Limited, 40 Broadwater Road, Welwyn Garden City, Hertfordshire, AL7 3AY, UK

    F. Brown & G. R. McClelland

Authors
  1. C. J. Kenyon
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  2. F. Brown
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  3. G. R. McClelland
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  4. I. R. Wilding
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Kenyon, C.J., Brown, F., McClelland, G.R. et al. The Use of Pharmacoscintigraphy to Elucidate Food Effects Observed with a Novel Protease Inhibitor (Saquinavir). Pharm Res 15, 417–422 (1998). https://doi.org/10.1023/A:1011972230829

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  • DOI: https://doi.org/10.1023/A:1011972230829

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