Abstract
Considerable work has been conducted on patients with CF to clearly demonstrate enhanced clearances of many, but not all drugs. The precise mechanisms for enhanced drug clearance in CF remain to be elucidated, and it will be important to examine the two major organs of drug elimination, the kidney and liver, for answers to these questions. Although it has not been studied to date, the role of the lung as a contributor to enhanced drug clearance in CF needs to be considered as well. In the liver it appears that both hepatic biotransformation as well as biliary excretion may be enhanced. In the kidney, there is enhanced CLr of acidic drugs, but variable findings for cationic and zwitterionic drugs. The latter finding can be explained on the basis of the pKa of the drugs and the urine pH. It would be most appealing if enhanced renal and nonrenal clearance of drugs in CF could be attributed to a common single defect. At this time, there is no obvious candidate, although altered transmembrane transport would represent a place to start.
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di Sant’Agnese, P. A. and Davis, P. B. (1979),Am. J. Med. 66, 121–132.
Boucher, R. and Beall, R. (1989),Pharmaceut. Res. 6, 525–527.
Youngberg, C. A., Berardi, R. R., Howatt, W. F., Hyneck, M. L., Amidon, G. L., Meyer, J. H., and Dressman, J. B. (1987),Digestive Dis. Sci. 32, 472–480.
Gaskin, K. J., Durie, P. R., Corey, M., Wei, P., and Forstner, G. G. (1982),Pediatr. Res. 16, 554–557.
Forstner, G., Gall, G., Corey, M., Durie, P., Hill, R., and Gaskin, K. (1980), inPerspectives in Cystic Fibrosis (Sturgess, J. M., ed.), Canadian Cystic Fibrosis Foundation, Toronto, Canada, pp. 137–148.
Park, R. W. and Grand, R. J. (1981),Gastroenterology 81, 1143–1161.
Bali, A., Stableforth, D. E., and Asquith, P. (1983),Brit. Med. J. 287, 1011–1013.
Milla, P. J., Rassam, U. B., Kilby, A., Ersser, R., and Harries, J. T. (1980), inPerspectives in Cystic Fibrosis (Sturgess, J. M., ed.), Proceedings of the 8th International Congress on Cystic Fibrosis, Toronto, Canada, pp. 177–180.
Frase, L. L., Strickland, A. D., Kachel, G. W., and Krejs, G. J. (1985),Gastroenterology 88, 478–484.
Buts, J. P., Morin, C. L., Roy, C. C, Weber, A., and Bonin, A. (1978),J. Pediatr. 92, 729–733.
Isles, A. F., Spino, M., Tabachnik, E., Levison, H., Thiessen, J. J., and MacLeod, S. M. (1983),Amer. Rev. Resp. Dis. 127, 417–421.
Spino, M., Chai, R. P., Isles, A. F., Thiessen, J. J., Tesoro, A., Gold, R., and MacLeod, S. M. (1984),J. Pediatr. 105, 829–835.
Durie, P. and Forstner, G. (198),J. Roy. Soc. Med. 82, 2–10.
Goldfarb, J., Wormser, G. P., Inchiosa, M. A., Guideri, G., Diaz, M., Gandhi, R., Goltzman, C, and Mascia, A. V. (1986),J. Clin. Pharmacol 26, 222–226.
Davis, R. L., Koup, J. R., Williams-Warren, J., Weber, A., Heggen, L., Stempel, D., and Smith, A. L. (1987),Antimicrob. Agents Chemother. 31, 915–919.
Reed, M. D., Stern, R. C, Myers, C. M., Yamashita, T. S., and Blumer, J. L. (1988), J.Clin. Pharmacol. 28, 691–699.
LeBel, M. (1988),Pharmacotherapy 8, 3–33.
Mimeault, J. B., Vallee, F., Seelmann, R., Sorgel, F., Ruel, M., and LeBel, M. (1990),Clin. Pharmacol. Ther. (in press).
Bentur, Y., Spino, M., Gold, R., Tesoro, M., Martin, S., Pop, R. D., Levy, M., and Heurter, H. (1990),Clin. Pharmacol. Ther. 47, 185.
Spino, M., Bentur, Y., Martin, S., Heurter, H., Brill-Edwards, M. A. T., Correia, J., Pop, R., Gold, R., and MacLeod, S. M. (1989),Eur. J. Clin. Pharmacol. 36, (Suppl): A84.
Dickinson, C, Reed, M., Stern, R., Aronoff, S., Yamashita, T., and Blumer, J. (1988),Pediatr. Res. 23, 388–392.
Turck, D., Boute, O., Ythier, H., Gottrand, F., Loeuille, G., and Farriaux, J. (1989),Arch. Fr. Pediatr. 46, 425–428.
Cooney, G. F., Fiel, S. B., Shaw, L. M., and Cavarocchi, N. C. (1989),Clin. Pharmacol Ther. 45, 140.
Gibaldi, M. and Perrier, D. (1982),Pharmacokinetics, Marcel Dekker, Inc., New York, pp. 319–353.
Knoppert, D. C, Spino, M., Beck, R., Thiessen, J. J., and MacLeod, S. M. (1988),Clin. Pharmacol. Ther. 44, 254–264.
Rowland, M. and Tozer, T. N. (1989),Clinical Pharmacokinetics: Concepts and Applications, (eds.): Lea and Febiger, Philadelphia, pp. 171–173.
Jusko, W. J., Mosovich, L. L., Gerbracht, L. M., Mattar, M. E., and Yaffe, S. J. (1975),Pediatrics 56, 1038–1044.
Yaffe, S. J., Gerbracht, L. M., Mosovich, L. L., Mattar, M. E., Danish, M., and Jusko, W. J. (1977),J. Infect. Dis. 135, 828–831.
Finkelstein, E. and Hall, K. (1979),J. Pediatr. 94, 163–164.
Levy, J., Smith, A. L., Koup, J. R., Williams-Warren, J., and Ramsey, B. (1984),J. Pediatr. 105, 117–124.
Kearns, G. L., Hilman, B. C, and Wilson, J. T. (1982),J. Pediatr. 100, 312–318.
Schachter, S. H., Spino, M., Isles, A. F., Tesoro, A., Prober, C, MacLeod, S. M., and Thiessen, J. J. (1983),Proc. 13th Int. Cong. Chemother. 7–12.
Leeder, J. S., Spino, M., Isles, A. F., Tesoro, A., Gold, R., and MacLeod, S. M. (1984),Clin. Pharmacol. Ther. 36, 355–362.
Hedman, A., Adan-abdi, Y., Alvan, G., and Strandvik, B. (1988),Clin. Phar macokinet. 15, 57–65.
Ziemniak, J. A., Assael, B. M., Padoan, R., and Schentag, J. J. (1984),Eur. J. Clin. Pharmacol. 26, 183–189.
Bosso, J. A., Saxon, B. A., Herbst, J. J., and Matsen, J. M. (1984),Antimicrob. Agents Chemother. 25, 630–632.
Michalsen, H. and Bergan, T. (1981),Antimicrob. Agents Chemother. 19, 1029–1031.
Prince, A. S. and Neu, H. C. (1980),J. Pediatr. 97, 148–151.
Guggenbichler, J. P. and Kienel, G. (1979),Monogr. Paediatr. 10, 34–40.
Nahata, M. C, Lubin, A. H., and Visconti, J. A. (1984),Dev. Pharmacol. Ther. 7, 221–228.
Thijssen, H. H. W. (1980),J. Chromatogr. 183, 339–345.
Arvidsson, A., Alvan, G., and Strandvik, B. (1983),Ada Paediatr. Scand. 72, 293–294.
Spino, M., Henderson, K., MacLeod, S. M., Correia, J., Koletzko, S., and Durie, P. (1988),Clin. Invest. Med. 11, 17.
Freiman, J., Chalmers, T., Smith, H., and Kuebler, R. (1978),N. Engl. J. Med. 299, 690–694.
Robson, A. M., Tateishi, S., Ingelfinger, J. R., Strominger, D. B., and Klahr, S. (1971),J. Pediatr. 79, 42–50.
Scott, J., Elias, E., Moult, P. J. A., Barnes, S., and Wills, M. R. (1977),Am. J. Med. 63, 488–492.
Allen, J. L. (1986),N. Engl. J. Med. 2, 764.
Rotellar, C, Mazzoni, M. J., Austin, H. A. III., Sabnis, S. G., Kulczycki, L., Rakowski, T. A., Mackow, R. C, and Winchester, J. F. (1989),Nephron 52, 178–182.
Michalsen, H., Monn, E., Bergan, T., Churg, J., and Johannessen, J. V. (1984),Path. Res. Pract. 178, 261–267.
Abramowsky, C. R. and Swinehart, G. L. (1982),Human Pathol. 13, 934–939.
Davis, C. A., Abramowsky, C. R., and Swinehart, G. (1984),Human Pathol. 15, 244–247.
Katz, S. M., Krueger, L. J., and Falkner, B. (1988),N. Engl. J. Med. 319, 263–266.
Sawchuk, R. J. and Rector, R. S. (1980),Clin. Pharmacokinets 5, 548–556.
Grantham, J. J. and Chonko, A. M. (1986),The Kidney (Brenner, B. M. and Rector, F. C, Jr., eds.), W. B. Saunder, Toronto, pp. 663–700.
Al-Awqati, Q., Chase, H. S., and Kleyman, T. R. (1986),The Kidney (Brenner, B. M. and Rector, F. C, Jr., eds.), W. B. Saunder, Toronto, pp. 61–89.
Ristuccia, A. M. (1984),Antimicrobial Therapy (Ristuccia, A. M. and Cunha, B. A., eds.) Raven, New York, pp. 305–328.
Spino, M., Chai, R. P., Isles, A. F., Balfe, J. W., Brown, R. G., Thiessen, J. J., and MacLeod, S. M. (1985),J. Pediatr. 107, 64–70.
Irish, J. M. III and Grantham, J. J. (1981),The Kidney (Brenner, B. M. and Rector, F. C., eds.), W. B. Saunders, Philadelphia, pp. 625.
Berg, U., Kusoffsky, E., and Strandvik, B. (1982),Ada Paediatr. Scand. 71, 833–838.
Vogelstein, B., Kowarski, A. A., and Lietman, P. S. (1977),J. Pediatr. 91, 333–339.
Strandvik, B., Berg, U., Kallner, A., and Kusoffsky, E. (1989),J. Pediatr. 115, 242–250.
Bins, J. and Mattie, H. (1989),Br. J. Clin. Pharmac. 27, 291–294.
Steffens, T., Holohan, P., and Ross, C. (1989),Am. J. Physiol. 256, F596-F609.
Quinton, P. M. (1989),Clin. Chem. 35, 726–730.
Inui, K.-I., Okano, T., Takano, M., Saito, H., and Hori, R. (1984),Biochem. Biophys. Ada 769, 449–454.
Tamai, I., Tsuji, A., and Ken, Y. (1988),J. Pharmacol. Exp. Ther. 246, 338–344.
Mann, H. J., Canafax, D. M., Cipolle, R. J., Daniels, D. E., Zaske, D. E., and Warwick, W. J. (1985),Pediatr. Pulmonol. 1, 238–243.
Hendeles, L., Iafrate, R. P., Stillwell, P. C, and Mangos, J. A. (1987),J. Pediatr. 110, 303–310.
Autret, E., Marchand, S., Breteau, M., and Grenier, B. (1986),Eur. J. Clin. Pharmacol. 31, 79–63.
Marks, M. I. and Vose, A. (1978),Antimicrob. Agents Chemother. 13, 753–758.
Sande, M. A. and Mandell, G. L. (1980),The Pharmacological Basis of Therapeutics (Gilman, A. G., Goodman, L. S., and Gilman, A., eds.), Macmillan, New York, pp. 1162–1180.
DeGroot, R. and Smith, A. L. (1987),Clin. Pharmacokinets 13, 228–253.
Horrevorts, A., DeWitte, J., Degener, J., Dzoljic-Danilovic, G., Hop, W., and Kerrebijn, K. (1987),Chest. 92, 844–848.
Pickering, L. K and Rutherford, I. (1981),J. Pharmacol Exp. Ther. 217, 345–349.
Rabin, H. R., Harley, G. L., Bryan, L. E., and Elfring, G. L. (1980),Perspectives in Cysticic Fibrosis (Sturgess, J. M., ed.), Toronto, Canadian Cystic Fibrosis Foundation, pp. 370–375.
Craig, W. A. and Gerber, A. U. (1981),Drugs,22, (Suppl. 1), pp. 35–45.
Beaune, P. H. and Guengerich, F. P. (1988),Pharmac. Ther. 37, 193–211.
Benet, L. Z. and Sheiner, L. B. (1985),The Pharmacological Basis of Therapeutics (Gilman, A. G., Goodman, L. S., Rail, T. W., and Murad, F., eds.), Toronto, Collier Macmillan Canada, Inc., pp. 3–34.
Okey, A. B. (1990),Pharmac. Ther. 45, 241–298.
Sitar, D. S. (1989),Pharmac. Ther. 43, 363–375.
Andersen, D. H. and Hodges, R. G. (1946),Amer. J. Dis. Child. 72, 62–80.
Craig, J. M., Haddad, H., and Shwachman, H. (1957),Am. J. Dis. Child. 93, 357–369.
Isenberg, J. N. (1982),Semin. Liver Dis. 2, 302–313.
Miller, C. A., Slusher, L. B., and Vesell, E. S. (1985),J. Clin. Invest. 75, 1415–1425.
Campbell, M. E., Grant, D. M., Inaba, T., and Kalow, W. (1987),Drug Metab. Disposit. 15, 237–249.
Bradbear, R. A., Shepherd, R. W., Grice, J., O” Toole, J., and Roberts, R. K, (1982),J. Pediatr. 100, 325–327.
Healy, D. P., Polk, R. E., Kanawati, L., Rock, D. T., and Mooney, M. L. (1989),Antimicrob. Agents Chemother. 33, 474–478.
Hultcrantz, R., Mengarelli, S., and Strandvik, B. (1986),Hepatology 6, 881–889.
Braganza, J. M. (1986),Med. Hypotheses 20, 233–243.
Kearns, G. L., Mallory, G. B., Crom, W. R., and Evans, W. E. (1988),Clin. Pharmacol. Ther. 43, 130.
Burczynski, F. J., Pushka, K. L., Sitar, D. S., and Greenway, C. V. (1987),Am. J. Physiol. 252, H953-H962.
Meuldermans, W., Van Peer, A., Hendricks, J., Lauwers, W., Swysen, E., Bock, M., Woestenborghs, R., and Heykants, J. (1988),Drug Metab. Disposit. 16, 403–409.
Kupfer, A., Schmid, B., and Pfaff, G. (1986),Xenobiotica 16, 421–433.
Bosso, J. A. and Evans, W. E. (1989),Clin. Pharmacol Ther. 45, 138.
Kerem, B-S., Rommens, J. M., Buchanan, J. A., Markiewicz, D., Cox, T. K., Chakravarti, A., Buchwald, M., and Tsui, L.-P. (1989),Science 245, 1073–1080.
Wilkinson, G. R. (1987),Pharmacol Rev. 39, 1–47.
Vergesslich, K., Gotz, M., Mostbeck, G., Sommer, G., and Ponhold, W. (1989),Pediatr. Radiol. 19, 371–374.
Weizman, Z., Durie, P. R., Kopelman, H. R., Vesely, S. M., and Forstner, G. G. (1986),Gut 27, 1043–1048.
Weber, A. M. and Roy, C. C. (1985),Ada Ped. Scand. (Suppl.)317, 9–15.
Jusko, W. J. and Gretch, M. (1976),Drug Metab. Rev. 5, 43–140.
Shwachman, H. and Kulczycki, L. L. (1958),Am. J. Dis. Child. 96, 6–15.
Taussig, L. M., Kattwinkel, J., Friedewald, W. T., and di Sant”Agnese, P. A. (1973),J. Pediatr. 82, 380–390.
MacDonald, N. E., Anas, N. G, Peterson, R. G, Schwartz, R. H., Brooks, J. G, and Powell, K. R. (1983),J. Pediatr. 103, 985–990.
Strandvik, B., Malmborg, A.-S., Bergan, T., Michalsen, H., Storrosten, O. T., and Wretlind, B. (1988),J. Antimicrob. Chemother. 21, 471–480.
Spino, M., Thiessen, J. J., Isles, A., Levison, H., and MacLeod, S. M. (1981),Pediatrics 68, 601, 602.
LeBel, M., Bergeron, M. G, Vallee, F., Fiset, C, Chasse, G, Bigonesse, P., and Rivard, G (1986),Antimicrob. Agents Chemother. 30, 260–266.
Zarowitz, B. J., Pilla, A. M., and Popovich, J. Jr. (1990),Clin. Pharm. 9, 40–44.
Homeida, M., Karrar, Z. A., and Roberts, C. J. C. (1979),Arch. Dis. Child. 54, 299–302.
Kappas, A., Anderson, K. E., Conney, A. H., and Alvares, A. P. (1976),Clin. Pharmacol. Ther. 20, 643–653.
Dodge, J. A. (1985),Acta Paediatr. Scand. (Suppl.) 317, 31–37.
Durie, P. R. and Pencharz, P. B. (1989),J. Roy. Soc. Med. 62, 11–20.
Anderson, K. E., Conney, A. H., and Kappas, A. (1979),Clin. Pharmacol. Ther. 26, 493–501.
Pantuck, E. J., Pantuck, C. B., Anderson, K. E., Wattenberg, L. W., Conney, A. H., and Kappas, A. (1984),Clin. Pharmacol. Ther. 35, 161–169.
Harrison, Y. E. and West, W. L. (1971),Biochem. Pharmacol. 20, 2105–2108.
Barbero, G. J. (1982),J. Pediatr. 100, 914, 915.
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Spino, M. Pharmacokinetics of drugs in cystic fibrosis. Clinical Reviews in Allergy 9, 169–210 (1991). https://doi.org/10.1007/BF02914541
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DOI: https://doi.org/10.1007/BF02914541