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Comparative pharmacokinetics of aminoglycoside antibiotics

1991; Wiley; Volume: 14; Issue: 1 Linguagem: Inglês

10.1111/j.1365-2885.1991.tb00801.x

1365-2885

Scott A. Brown, Jim E. Riviere,

Veterinary medicine and infectious diseases

Journal of Veterinary Pharmacology and TherapeuticsVolume 14, Issue 1 p. 1-35 Comparative pharmacokinetics of aminoglycoside antibiotics S. A. BROWN, S. A. BROWN Clinical Pharmacology Laboratory, Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, Texas 77843 *Worldwide Animal Health Clinical Development, 9690-190-40, The Upjohn Company, Kalamazoo, Michigan 49001, USA.Search for more papers by this authorJ. E. RIVIERE, J. E. RIVIERE Laboratory of Toxicokinetics, Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USASearch for more papers by this author S. A. BROWN, S. A. BROWN Clinical Pharmacology Laboratory, Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, Texas 77843 *Worldwide Animal Health Clinical Development, 9690-190-40, The Upjohn Company, Kalamazoo, Michigan 49001, USA.Search for more papers by this authorJ. E. RIVIERE, J. E. RIVIERE Laboratory of Toxicokinetics, Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USASearch for more papers by this author First published: March 1991 https://doi.org/10.1111/j.1365-2885.1991.tb00801.xCitations: 40 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat REFERENCES Adelman, M., Evans, E.E. & Schentag, J.J. (1982) Two-compartment comparison of gentamicin and tobramycin in normal volunteers. Antimicrobial Agents and Chemotherapy, 22, 800–804. Al-Guedawy, S.A., Neff-Davis, C.A., Davis, L.E., Whitmore, H.L. & Gustafsson, B.K. (1983) Disposition of gentamicin in the genital tract of cows. Journal of Veterinary Pharmacology and Therapeutics, 6, 85–92. Andreini, G. & Pignatelli, P. (1972) Kanamycin blood levels and residues in domestic animals. Veterinaria, 21, 51–72. Aronoff, G.R., Pottratz, S.T., Brier, M.E. et al. (1983) Aminoglycoside accumulation kinetics in rat renal parenchyma. Antimicrobial Agents and Chemotherapy, 23, 74–78. Baggot, J.D. (1977) Principles of Drug Disposition in Domestic Animals. Philadelphia , WB Saunders Co. Baggot, J.D. (1978) Pharmacokinetics of kanamycin in dogs. Journal of Veterinary Pharmacology and Therapeutics, 1, 163–170. Baggot, J.D., Ling, G.V. & Chatfield, R.C. (1985) Clinical pharmacokinetics of amikacin in dogs. American Journal of Veterinary Research, 46, 1793–1796. Baggot, J.D., Love, D.N., Rose, R.J. & Raus, J. (1981) The pharmacokinetics of some aminoglycoside antibiotics in the horse. Journal of Veterinary Pharmacology and Therapeutics, 4, 277–284. Batra, V.K., Morrison, J.A. & Hoffman, T.R. (1983) Pharmacokinetics of piperacillin and gentamicin following intravenous administration to dogs. Journal of Pharmaceutical Sciences, 72, 894–898. Bauer, L.A. & Blouin, R.A. (1981) Influence of age on tobramycin pharmacokinetics in patients with normal renal function. Antimicrobial Agents and Chemotherapy, 20, 587–589. Bennett, W.M., Plamp, C.E., Gilbert, D.N., Parker, R.A. & Porter, G.A. (1979) The influence of dosage regimen on experimental gentamicin nephrotoxicity: dissociation of a peak serum level from renal failure. Journal of Infectious Diseases, 140, 576–580. Bergeron, M.G., Bastille, A., Lessard, C. & Gagnon, P.M. (1982a) Significance of intrarenal concentrations of gentamicin for the outcome of experimental pyelonephritis in rats. Journal of Infectious Diseases, 146, 91–96. Bergeron, M.G. & Bergeron, Y. (1986) Influence of endotoxin on the intrarenal distribution of gentamicin, netilmicin, tobramycin, amikacin, and cephalothin. Antimicrobial Agents and Chemotherapy, 29, 7–12. Bergeron, M.G., Bergeron, Y. & Beauchamp, D. (1987) Influence of hydrocortisone succinate on intrarenal accumulation of gentamicin in endo-toxemic rats. Antimicrobial Agents and Cliemo-therapy, 31, 1816–1821. Bergeron, M.G., Trottier, S., Lessard, C., Beauchamp, D. & Gagnon, P.M. (1982b) Disturbed intrarenal distribution of gentamicin in experimental pyelonephritis due to Escherichia coli. Journal of Infectious Diseases, 146, 436–439. Bille, J. & Glauser, M.P. (1981) Prophylaxis of pyelonephritis by aminoglycosides accumulated in the kidney. Journal of Antimicrobial Chemotherapy, 8 (Suppl. A), 115–119. Bird, J.E., Miller, K.W., Larson, A.A. & Duke, G.E. (1983) Pharmacokinetics of gentamicin in birds of prey. American Journal of Veterinary Research, 44, 1245–1247. Black, J., Calesnick, B., Williams, D. & Weinstein, M.J. (1964) Pharmacology of gentamicin, a new broad-spectrum antibiotic. Antimicrobial Agents and Chemotherapy, 3, 138–147. Black, W.D., Holt, J.D. & Gentry, R.D. (1983) Pharmacokinetic study of neomycin in calves following intravenous and intramuscular administration. Canadian Journal of Comparative Medicine, 47, 433–435. Blaser, J., Rieder, H., Niederer, P. & Lttthy, R. (1983) Biological variability of multiple dose pharmacokinetics of netilmicin in man. European Journal of Clinical Pharmacology, 24, 359–406. Blaser, J., Simmon, H.P., Gonzenbach, H.R., Sonnabend, W. & Lüthy, R. (1985) Aminoglycoside monitoring: Timing of peak levels is critical. Therapeutic Drug Monitoring, 7, 303–307. Bowman, K.F., Dix, L.P., Riond, J.-L. & Riviere, J.E. (1986) Prediction of pharmacokinetic profiles of ampicillin sodium, gentamicin sulfate, and combination ampicillin sodium-gentamicin sulfate in serum and synovia of healthy horses. American Journal of Veterinary Research, 47, 1590–1596. Brasseur, R., Laurent, G., Ruysschaert, J.M. & Tulkens, P. (1984) Interactions of aminoglycoside antibiotics with negatively charged lipid layers. Biochemical Pharmacology, 33, 629–637. Brier, M.E., Mayer, P.R., Brier, R.A., Visscher, D., Luft, F.C. & Aronoff, G.R. (1985) Relationship between rat renal accumulation of gentamicin, tobramycin, and netilmicin and their nephrotoxicities. Antimicrobial Agents and Chemotherapy, 27, 812–816. Brown, M.P., Stover, S.M., Kelly, R.H. & Farver, T.B. (1981) Kanamycin sulfate in the horse: serum, synovial fluid, peritoneal fluid, and urine concentrations after single-dose intramuscular administration. American Journal of Veterinary Research, 42, 1823–1825. Brown, M.P., Embertson, R.M., Gronwall, R.R., Beal, C., Mayhew, I.G. & Curry, S.H. (1984) Amikacin sulfate in mares: pharmacokinetics and body fluids and endometrial concentrations after repeated intramuscular administration. American Journal of Veterinary Research, 45, 1610–1613. Brown, S.A. & Baird, A.N. (1988) Evaluation of renal gentamicin depletion kinetic properties in sheep, using serial percutaneous biopsies. American Journal of Veterinary Research, 49, 2056–2059. Brown, S.A., Coppoc, G.L. & Riviere, J.E. (1986a) Effects of dose and duration of therapy on gentamicin tissue residues in sheep. American Journal of Veterinary Research, 47, 2373–2379. Brown, S.A., Coppoc, G.L., Riviere, J.E. & Anderson, V.L. (1986b) Dose-dependent pharmacokinetics of gentamicin in sheep. American Journal of Veterinary Research, 47, 789–794. Brown, S.A. & Garry, F.B. (1988) Comparison of serum and renal gentamicin concentrations and fractional urinary excretion tests as indicators of nephrotoxicity. Journal of Veterinary Pharmacology and Therapeutics, 11, 330–337. Brown, S.A., Nelson, R.W. & Scott-Moncrieff, C. (1991) Pharmacokinetics of gentamicin in diabetic dogs. Journal of Veterinary Pharmacology and Therapeutics, 14, (in press). Brown, S.A., Riviere, J.E. & Coppoc, G.L. (1981) Pharmacokinetics and tissue disposition of gentamicin in sheep. Proceedings of the Conference of Research Workers in Animal Disease, 62, 15. Brown, S.A., Riviere, J.E., Coppoc, G.L. & Dix, L.P. (1986c) Superiority of the power function over exponential functions for prediction of renal gentamicin residues in sheep. Journal of Veterinary Pharmacology and Therapeutics, 9, 341–346. Brown, S.A., Riviere, J.E., Coppoc, G.L., Hinsman, E.J., Carlton, W.W. & Steckel, R.R. (1985) Single intravenous and multiple intramuscular dose pharmacokinetics and tissue residue profile of gentamicin in sheep. American Journal of Veterinary Research, 46, 69–74. Buchanan, N., Davis, M.D. & Eyberg, C. (1979) Gentamicin pharmacokinetics in kwashiorkor. British Journal of Clinical Pharmacy, 8, 451–453. Burrows, G.E., Barto, P.B. & Martin, B. (1986) Antibiotic disposition in experimental pneumonic pasteurellosis: gentamicin and tylosin. Canadian Journal of Veterinary Research, 50, 193–199. Bush, M., Locke, D., Neal, L.A. & Carpenter, J.W. (1981) Gentamicin tissue concentrations in various avian species following recommended dosage therapy. American Journal of Veterinary Research, 42, 2114–2116. Cabana, B.E. & Taggart, J.G. (1973) Comparative pharmacokinetics of BB-K8 and kanamycin in dogs and humans. Antimicrobial Agents and Chemotherapy, 3, 478–483. Carbon, C., Contrepois, A. & Lamotte-Barillon, S. (1978) Comparative distribution of gentamicin, tobramycin, sisomicin, netilmicin, and amikacin in interstitial fluid in rabbits. Antimicrobial Agents and Chemotherapy, 13, 368–372. Charuel, C., Faceini, J., Monro, A. & Nachbaur, J. (1984) A second peak in uptake of gentamicin by rat kidney after cessation of treatment. Bio-pharmaceutics and Drug Disposition, 5, 21–24. Chisholm, G.D., Calnan, J.S., Waterworth, P.M. & Reis, N.D. (1968) Distribution of gentamicin in body fluids. British Medical Journal, 2, 22–24. Chiu, P.T.S., Brown, A., Miller, G. et al. (1976) Renal extraction gentamicin in anesthetized dogs. Antimicrobial Agents and Chemotherapy, 10, 277–282. Chiu, P.T.S. & Long, J.F. (1978) Effects of hydration on gentamicin excretion and renal accumulation in furosemide-treated rats. Antimicrobial Agents and Chemotherapy, 14, 214–217. Chiu, P.T.S., Miller, G.H., Long, J.F. & Waitz, J.A. (1979) Renal uptake and nephrotoxicity of gentamicin during urinary alkalinization in rats. Clinical and Experimental Pharmacology and Physiology, 6, 317–326. Chung, M., Costello, R. & Symchowitz, S. (1980) Comparison of netilimicin and gentamicin pharmacokinetics in humans. Antimicrobial Agents and Chemotherapy, 17, 184–187. Chung, M., Parravicini, L., Assael, B.M., Cavanna, G., Radwanski, E. & Symchowicz, S. (1982) Comparative pharmacokinetics of aminoglycoside antibiotics in guinea pigs. Antimicrobial Agents and Chemotherapy, 22, 1017–1021. Clarke, C.R., Short, C.R., Hsu, R.-C. & Baggot, J.D. (1985) Pharmacokinetics of gentamicin in the calf: Developmental changes. American Journal of Veterinary Research, 46, 2461–2466. Colburn, W.A., Schentag, J.J., Jusko, W.J. & Gibaldi, M. (1978) A model for the prospective identification of the prenephrotoxic state during gentamicin therapy. Journal of Pharmacokinetics and Biopharmaceutics, 6, 179–186. Contrepois, A., Brion, N., Girard, J.-J. et al. (1985) Renal disposition of gentamicin, dibekacin, tobramycin, netilmicin, and amikacin in humans. Antimicrobial Agents and Chemotherapy, 27, 520–524. Cowan, R.H., Jukkola, A.F. & Arant, B.S. (1980) Pathophysiologic evidence of gentamicin nephrotoxicity in neonatal puppies. Pediatric Research, 14, 1204–1211. Custer, R.S., Bush, M. & Carpenter, J.W. (1979) Pharmacokinetics of gentamycin in blood plasma of quail, pheasants and cranes. American Journal of Veterinary Research, 40, 892–895. Cutler, R.E., Gyselynck, A.-M., Fleet, W.P. & Forrey, A.W. (1972) Correlation of serum creatinine concentration and gentamicin half-life. Journal of the American Medical Association, 219, 1037–1041. Desrochers, C.S. & Schacht, J. (1982) Neomycin concentrations in inner ear tissues and other organs of the guinea pig after chronic drug administration. Acta Otolaryngologica, 93, 233–236. Dickson, P.L., DiPiro, J.T., Michael, K.A., Cheung, R.P.F. & Hall, E.M. (1987) Effect of hemorrhagic shock on cefazolin and gentamicin pharmacokinetics in dogs. Antimicrobial Agents and Chemotherapy, 31, 389–392. Drury, A.R. (1952) Evaluation of neomycin sulfate in treatment of bovine mastitis. Veterinary Medicine, 47, 407–411. Dulon, D., Aran, J.-M., Zajic, G. & Schacht, J. (1986) Comparative uptake of gentamicin, netilmicin, and amikacin in the guinea pig cochlea and vestibule. Antimicrobial Agents and Chemotherapy, 30, 96–100. Dyas, A., Wise, R., Pijck, J. et al. (1983) Reproducibility study of the pharmacokinetics of amikacin, gentamicin and tobramycin; a three-way crossover study. Journal of Antimicrobial Chemotherapy, 12, 371–376. Edgren, B., Kama, P., Sciamanna, D. & Dolanski, E. (1983) Gentamicin dosing in the newborn. Use of a one-compartment open pharmacokinetic model to individualize dosing. Developmental Pharmacology and Therapeutics, 7, 263–272. Edwards, D.J., Mangione, A., Cumbo, T.J. & Schentag, J.J. (1981) Predicted tissue accumulation of netilmicin in patients. Antimicrobial Agents and Chemotherapy, 20, 1714–717. Evans, W.E., Taylor, R.H., Feldman, S., Crom, W.R., Rivera, G. & Yee, G.C. (1980) A model for dosing metamicin in children and adolescents that adjusts for tissue accumulation with continuous dosing. Clinical Pharmacokinetics, 5, 295–306. Fabre, J., Rudhardt, M., Blanchard, P. & Regamey, C. (1976) Persistence of sisomicin and gentamicin in renal cortex and medulla compared with other organs and serum of rats. Kidney International, 10, 444–449. Fabre, J. (1980) Aminoglycoside nephrotoxicity. Néphrologie, 1, 37–43. Faragó, E. & Guba, T. (1988) A study of the levels of tobramycin and gentamicin in human serum and renal cortex and of changes in in vitro bacterial sensitivity. International Journal of Clinical Pharmacology, Therapy, and Toxicology, 26, 199–203. Follath, F., Spring, P., Wenk, M., Benet, L.Z. & Dettli, L. (1978) Comparative pharmacokinetics of sisomicin and netilmicin in healthy volunteers. Current Chemotherapy, 2, 979–980. Follath, F., Vozeh, S. & Wenk, M. (1982) Pharmacokinetic models and dosage regimens. In Pharmacokinetics. Ed. H. Gladtke pp. 109–115. Gustav Fischer Verlag, New York . Frazier, D.L., Aucoin, D.P. & Riviere, J.E. (1988) Gentamicin pharmacokinetics and nephrotoxicity in naturally acquired and experimentally induced disease in dogs. Journal of the American Veterinary Medical Association, 192, 57–63. Frazier, D.L. & Riviere, J.E. (1987) Gentamicin dosing strategies for dogs with subclinical renal dysfunction. Antimicrobial Agents and Chemotherapy, 31, 1929–1934. Gemer, O., Zaltztein, E. & Gorodischer, R. (1983) Absorption of orally administered gentamicin in infants with diarrhea. Pediatric Pharmacology, 3, 119–123. Gerber, A.U., Craig, W.A., Brugger, H.-P., Feller, C., Vastola, A.P. & Brandel, J. (1983) Impact of dosing intervals on activity of gentamicin and ticarcillin against Pseudomonas aeruginosa in granulocytopenic mice. Journal of Infectious Diseases, 147, 910–917. Gilman, J.M., Davis, L.E., Neff-Davis, C.A., Koritz, G.D. & Baker, G.J. (1987) Plasma concentrations of gentamicin after intramuscular or subcutaneous administration to horses. Journal of Veterinary Pharmacology and Therapeutics, 10, 101–103. Goodman, E.L., Van Gelder, J., Holmes, R., Hull, A.R. & Sanford, J.P. (1975) Prospective comparative study of variable dosage and variable frequency regimens for administration of gentamicin. Antimicrobial Agents and Chemotherapy, 8, 434–438. Guiliano, R.A., Verpooten, G.A., Verbist, L., Wedeen, R.P. & De Broe, M.E. (1986) In vivo uptake kinetics of aminoglycosides in the kidney cortex of rats. Journal of Pharmacology and Experimental Therapeutics, 236, 470–475. Gyselynck, A.M., Forrey, A. & Cutler, R.E. (1971) Pharmacokinetics of gentamicin: Distribution and plasma clearance. Journal of Infectious Diseases, 124 (Suppl.), S70–S76. Haddad, N.S., Pedersoli, W.M., Ravis, W.R., Fazeli, M.H. & Carson, RX. Jr (1985a) Pharmacokinetics of gentamicin at steady-state in ponies: Serum, urine, and endometrial concentrations. American Journal of Veterinary Research, 46, 1268–1271. Haddad, N.S., Pedersoli, W.M., Ravis, W.R., Fazeli, M.H. & Carson, R.L. Jr (1985b) Combined pharmacokinetics of gentamicin in pony mares after a single intravenous and intramuscular administration. American Journal of Veterinary Research, 46, 2004–2007. Haddad, N.S., Ravis, W.R., Pedersoli, W.M. & Carson, R.L. Jr (1986) Pharmacokinetics of single doses of gentamicin given by intravenous and intramuscular routes to lactating cows. American Journal of Veterinary Research, 47, 808–813. Haddad, N.S., Ravis, W.R., Pedersoli, W.M. & Carson, R.L., Jr. (1987) Pharmacokinetics and tissue residues of gentamicin in lactating cows after multiple intramuscular doses are administered. American Journal of Veterinary Research, 48, 21–27. Halkin, H., Lidji, M. & Rubenstein, E. (1981) The influence of endotoxin-induced pyrexia on the pharmacokinetics of gentamicin in the rabbit. Journal of Pharmacology and Experimental Therapeutics, 216, 415–418. Hammond, P.B. (1953) Dihydrostreptomycin dose-serum level relationships in cattle. Journal of the American Veterinary Medical Association, 122, 203–206. Hauser, G. & Eichberg, J. (1973) Improved conditions for the preservation and extraction of polyphosphoinositides. Biochimica et Biophysio-logica Acta, 326, 201–209. Heissler, J. & Pancorbo, S. (1980) Comparison of gentamicin and tobramycin nephrotoxicity in patients receiving individualized pharmacokinetic dosing regimens. American Society of Hospital Pharmacy Midyear Clinical Meeting, San Francisco, p. 217. Herscovici, L., Lemeland, J.F., Dalion, J., Olier, B. & Fillastre, J.P. (1984) Acute experimental pyelonephritis. Treatment with tobramycin. Influence of the rhythm of administration on efficacy and renal tolerability. Pathologic Biology (Paris), 32, 450–454. Holohan, P.D., Elliott, W.C., Grace, E. & Ross, C.R. (1987) Effect of parathyroid hormone on gentamicin plasma membrane binding and tissue accumulation. Journal of Pharmacology and Experimental Therapeutics, 243, 893–986. Huang, S.-M., Huang, Y.-C. & Chiou, W.L. (1979) Triexponential disposition pharmacokinetics of gentamicin in rabbits. Research Communications in Chemical Pathology and Pharmacology, 261, 115–127. Huber, W.G. (1982) Aminoglycosides, macrolides, lincosamides, polymyxins, chloramphenicol, and antibacterial drugs. In Veterinary Pharmacology and Therapeutics, 5th edn. Eds. N.H. Booth & L.E. McDonald pp. 748–756. Iowa State University Press, Ames , IA . Hunter, R.P., Brown, S.A., Rollins, J.K. & Nelligan, D.F. (1991) The effects of experimentally induced bronchopneumonia on the pharmacokinetics and tissue depletion of gentamicin in calves. Journal of Veterinary Pharmacology and Therapeutics, 14, (in press). Jacobson, E.R., Groff, J.M., Gronwall, R.R., More-land, A.F. & Chung, M. (1985) Serum concentrations of gentamicin in cats. American Journal of Veterinary Research, 46, 1356–1358. Jahre, J.A., Fu, K.P. & Neu, H.C. (1978) Kinetics of netilmicin and gentamicin. Clinical Pharmacology and Therapeutics, 23, 591–597. Jawetz, E. (1984) Aminoglycosides and polymyxins. In Basic and Clinical Pharmacology, 2nd edn. Ed. B.G. Katzung pp. 538–545. Lange Medical Publications, Los Altos , CA . Jernigan, A.D., Hatch, R.C., Brown, J. & Crowell, W.A. (1988a) Pharmacokinetic and pathological evaluation of gentamicin in cats given a small intravenous dose repeatedly for five days. Canadian Journal of Veterinary Research, 52, 177–180. Jernigan, A.D., Hatch, R.C. & Wilson, R.C. (1988b) Pharmacokinetics of tobramycin in cats. American Journal of Veterinary Research, 49, 608–612. Jernigan, A.D., Hatch, R.C., Wilson, R.C., Brown, J. & Crowell, W.A. (1988c) Pathologic changes and tissue gentamicin concentrations after intravenous gentamicin administration in clinically normal and endotoxemic cats. American Journal of Veterinary Research, 49, 613–617. Jernigan, A.D., Hatch, R.C., Wilson, R.C., Brown, J. & Tuler, S.M. (1988d) Pharmacokinetics of gentamicin in cats given Escherichia coli endotoxin. American Journal of Veterinary Research, 49, 603–607. Jernigan, A.D., Wilson, R.C. & Hatch, R.C. (1988e) Pharmacokinetics of amikacin in cats. American Journal of Veterinary Research, 49, 355–358. Jernigan, A.D., Wilson, R.C., Hatch, R.C. & Kemp, D.T. (1988f) Pharmacokinetics of gentamicin after intravenous, intramuscular, and subcutaneous administration in cats. American Journal of Veterinary Research, 49, 32–35. Johansson, P., Josefsson, J.O. & Nassberger, L. (1984) Induction and inhibition of pinocytosis by aminoglycoside antibiotics. British Journal of Pharmacology, 83, 615–623. Josepovitz, C., Levine, R., Farraggulla, T., Lane, B. & Kaloyanides, G.J. (1985) [3H]netilmicin binding constants and phospholipid composition of renal plasma membranes of normal and diabetic rats. Journal of Pharmacology and Experimental Therapeutics, 233, 298–303. Josepovitz, C., Pastoriza-Munoz, E., Timmerman, D., Scott, M., Feldman, S. & Kaloyanides, G.J. (1982) Inhibition of gentamicin uptake in rat renal cortex in vivo by aminoglycosides and organic polycations. Journal of Pharmacology and Experimental Therapeutics, 223, 314–321. Kahlmeter, G. (1979) Nephrotoxicity of gentamicin. Scandinavian Journal of Infectious Diseases, 11 (Suppl.), 15–40. Kahlmeter, G., Jonsson, S. & Kamme, C. (1978) Multiple-compartment pharmacokinetics of tobramycin. Journal of Antimicrobial Chemotherapy, 4 (Suppl. A), 5–11. Kahlmeter, G. & Kamme, C. (1975) Prolonged excretion of gentamicin in a patient with impaired renal function. Lancet, i, 286. Katzung, B.G. (1984) Introduction. In Basic and Clinical Pharmacology, 2nd edn. Ed. B.G. Katzung p. 2. Lange Medical Publications, Los Altos , CA . Kaye, D., Levison, M.E. & Labovitz, E.D. (1974) The unpredictability of serum concentrations of gentamicin: pharmacokinetics of gentamicin in patients with normal and abnormal renal function. Journal of Infectious Diseases, 130, 150–154. Kirschbaum, B.B. (1984) Interactions between renal brush border membranes and polyamines. Journal of Pharmacology and Experimental Therapeutics, 229, 409–416. Kluwe, W.M. & Hook, J.B. (1978) Analysis of gentamicin uptake by rat renal cortical slices. Toxicology and Applied Pharmacology, 45, 531–539. Kuhar, M.J., Mak, L.L. & Lietman, P.S. (1979) Autoradiographic localization of [3H]gentamicin in the proximal renal tubules of mice. Antimicrobial Agents and Chemotherapy, 15, 131–133. Kusumi, R., Metzler, C. & Fass, R. (1981) Pharmacokinetics of spectinomycin in volunteers with renal insufficiency. Chemotherapy, 27, 95–98. Laskin, O.L., Longstreth, L.A., Smith, C.R. & Lietman, P.S. (1983) Netilmicin and gentamicin multidose kinetics in normal subjects. Clinical Pharmacology and Therapeutics, 34, 644–650. LeCompte, J., Dumont, L., DuSouich, P. & LeLorier, J. (1981) Effect of water deprivation and rehydration on gentamicin disposition in the rat. Journal of Pharmacology and Experimental Therapeutics, 218, 231–236. Lee, M.G., Chen, M.-L., Huang, S.-M. & Chiou, W.L. (1981) Pharmacokinetics of drugs in blood. I. Unusual distribution of gentamicin. Biopharma-ceutics and Drug Disposition, 2, 89–97. Lelievre-Pegorier, M., Sagly, R., Meulemans, A. & Merlet-Benichou, C. (1985) Kinetics of gentamicin in plasma of nonpregnant, pregnant, and fetal guinea pigs and its distribution in fetal tissues. Antimicrobial Agents and Chemotherapy, 28, 565–569. Ling, G.V., Conzelman, G.M., Franti, C.E. & Ruby, A.L. (1981) Urine concentrations of gentamicin, tobramycin, amikacin, and kanamycin after subcutaneous administration to healthy dogs. American Journal of Veterinary Research, 42, 1792–1794. Luft, F.C., Bloch, R., Sloan, R.S., Yum, M.N., Costello, R. & Maxwell, D.R. (1978) Comparative nephrotoxicity of aminoglycoside antibiotics in ruts. Journal of Infectious Diseases, 138, 541–545. Luft, F.C. & Kleit, S.A. (1974) Renal parenchymal accumulation of aminoglycoside antibiotics in rats. Journal of Infectious Diseases, 130, 656–659. McMartin, D.N. & Engel, S.G. (1982) Effect of aging on gentamicin nephrotoxicity and pharmacokinetics in rats. Research Communications in Chemical Pathology and Pharmacology, 38, 193–207. Mader, D.R., Conzelman, G.M. Jr & Baggot, J.D. (1985) Effects of ambient temperature on the half-life and dosage regimen of amikacin in the gopher snake. Journal of the American Veterinary Medical Association, 187, 1134–1136. Mann, H.J., Fuhs, D.W., Awang, R., Ndemo, F.A. & Cerra, F.B. (1987) Altered aminoglycoside pharmacokinetics in critically ill patients with sepsis. Clinical Pharmacy, 6, 148–153. Marre, R., Tarara, N., Louton, T. & Sack, K. (1980) Age-dependent nephrotoxicity and the pharmacokinetics of gentamicin in rats. European Journal of Pediatrics, 133, 25–29. Mercer, H.D., Rollins, K.D., Garth, M.A. & Carter, G.G. (1971) A residue study and comparison of penicillin and dihydrostreptomycin concentrations after intramuscular and subcutaneous administration in cattle. Journal of the American Veterinary Medical Association, 158, 776–779. Miranda, J.C., Schimmel, M.S., Mimms, G.M. et al. (1984) Gentamicin absorption during prophylactic use for necrotizing enterocolitis. Development Pharmacology and Therapeutics, 7, 303–306. Moore, R.D., Smith, C.R. & Lietman, P.S. (1984) Association of aminoglycoside plasma levels with therapeutic outcome in gram-negative pneumonia. American Journal of Medicine, 77, 657–662. Nouws, J.F.M. & Ziv, G. (1977) Tissue distribution and residues of aminoglycoside antibiotics in normal dairy cows. Tijdschrift voor Diergeneeskunde, 102, 1187–1193. Nouws, J.F.M. & Ziv, G. (1978) Tissue distribution and residues of benzylpenicillin and aminoglycoside antibiotics in emergency-slaughtered ruminants. Tijdschrift voor Diergeneeskunde, 103, 140–151. Olier, B., Viotte, G., Morin, J.P. & Fillastre, J.P. (1983) Influence of dosage regimen on experimental tobramycin nephrotoxicity. A biochemical approach. Chemotherapy, 29, 385–394. Orme, B.M. & Cutler, R.E. (1969) The relationship between kanamycin pharmacokinetics: distribution and renal function. Clinical Pliarmacology and Therapeutics, 10, 543–550. Orsini, J.A., Soma, L.R., Rourke, J.E. & Park, M. (1985) Pharmacokinetics of amikacin in the horse following intravenous and intramuscular administration. Journal of Veterinary Pharmacology and Therapeutics, 8, 194–201. Pastoriza-Munoz, E., Josepovitz, C., Ramsammy, L. & Kaloyanides, G.J