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May also be of value in some populations, as well as in situations where very accurate assessment of phenotype is available to validate any prediction of outcome.115 A large number of drugs can be metabolized by CYP2D6. However, the drugs for which this approach will be most valuable will be those that are predominantly metabolized by CYP2D6 or those in which metabolism to important, active metabolites is catalyzed exclusively or primarily by CYP2D6. The clinical value of CYP2D6 genotyping will be most valuable when it provides a significant incremental improvement over what can currently be predicted by use of routinely available clinical tests. As a result, its impact will likely be greatest in oncology and in psychiatry, in which the existing means of predicting effect are limited. It is difficult for care providers who treat patients who are depressed or have bipolar disorder to predict in advance which antidepressants or antipsychotics will work best in which patient, resulting in significant morbidity and mortality rates. Similarly, when the only assessment of the efficacy of antitumor therapy is the return of metastatic disease, it is clear that public health could benefit greatly from better methods of predicting outcome. Conclusions. Although we have been aware of the CYP2D6 genetic polymorphism for more than a quarter century, it remains the case that there is no situation in which testing for this polymorphism is in routine clinical practice. That being said, CYP2D6 genotyping is now an established and frequently used tool in drug development that is of great value in the determination of the effects of this important polymorphism on the pharmacokinetics of new molecular entities which undergo metabolism by the enzyme. In addition, FDA-approved testing is now available, an increasing number of companies provide CYP2D6 genotyping under Good Laboratory Practice conditions, and an increasing number of medical centers provide this service to patients under their care. It will be increasingly important for physicians, pharmacists, and other care providers to be able to provide coherent therapeutic recommendations to patients with predetermined pharmacogenetic data. UGT1A1 UGT1A1 has been shown to metabolize various drugs, 37 including SN-38, the active metabolite of irinotecan, 117 a cytotoxic agent approved for metastatic colorectal cancer usually administered in combination with 5-fluorouracil. It is also commonly used off-label for other solid tumors. ; Its use is limited by toxicity, including life-threatening neutropenia and associated infection, most common on the every-3-week schedule. The other major and cilexetil, because chloromycetin palmitate. 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All medications used for the treatment of hiv are on the formulary, if fda approved and ciloxan. Escherichia coli. J. Molecular Biol., 1, 301-320. 71. LOEWE, S. 1953 The problem of synergism and antagonism of combined drugs. Arzneimittel-Forsch., 3, 285-290. 72. MAGER, J. 1960 Chloramphenicol and chlortetracycline inhibition of amino acid incorporation into proteins in a cell-free system from Tetrahymena pyriformis. Biochim. et Biophys. Acta, 38, 150-152. 73. MANDELSTAM, J. 1958 The free amino acids in growing and non-growing populations of Escherichia coli. Biochem. J., 69, 103-110. 74. MANDELSTAM, J. 1958 Turnover of protein in growing and non-growing populations of Escherichia coli. Biochem. J., 69, 110-119. 75. MANDELSTAM, J. AND ROGERS, H. J. 1959 The incorporation of amino acids into the cell-wall mucopeptide of staphylococci and the effect of antibiotics on the process. Biochem. J., 72, 654-662. 76. MAXWELL, R. E. AND NICKEL, V. S. 1954 The antibacterial activity of the isomers of chloramphenicol. Antibiotics & Chemotherapy, 4, 289-295. 77. MCLEAN, I. W., JR., SCHWAB, J. L., HILLEGAS, A. B., AND SCHLINGMAN, A. S. 1949 Susceptibility of microorganisms to chloramphenicol Chloromyfetin ; . J. Clin. Invest., 28, 953-963. 78. MERKEL, J. R. AND STEERS, E. 1953 The relationship between "chloramphenicol reductase activity" and chloramphenicol resistance in Escherichia coli. J. Bacteriol., 66, 389-396. 79. PARDEE, A. B., PAIGEN, K., AND PRESTIDGE, L. S. 1957 A study of the ribonucleic acid of normal and Chloromycetin-inhibited bacteria by zone electrophoresis. Biochim. et Biophys. Acta, 23, 16 -173. 80. POMERAT, C. M. AND LEAKE, C. D. 1954 Short term cultures for drug assays: general considerations. Ann. N. Y. Acad. Sci., 68, 1110-1128. 81. PRESTIDGE, L. S. AND PARDEE, A. B. 1957 Induction of bacterial lysis by penicillin. J. Bacteriol., 74, 48-59. 82. PULVERTAFT, R. J. V. 1952 The effect of antibiotics on growing cultures of Escherichia coli. J. Pathol. Bacteriol., 64, 75-89. 83. RAMSEY, H. H. 1958 Protein synthesis as a basis for chloramphenicol-resistance in Staphylococcus aureus. Nature, 182, 602603. 84. REBSTOCK, M. C., CROOKS, H. M., CONTROULIS, J., AND BARTZ, Q. R. 1949.

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Nutrition and M.D. from the prestigious University of Michigan. After a five-year residency in OtolaryngologyHead and Neck Surgery at Henry Ford Health System HFHS ; in Bloomfield, Michigan, he completed a fellowship in Otologic Neurotologic and Skull Base Surgery at the Ear Research Foundation in Florida. Dr. Seidman is the Director of the Division of Otologic Neurotologic Surgery in the Department of OtolaryngologyHead and Neck Surgery for HFHS, Director of Otolaryngology Research Laboratory, the Co-Director of the Tinnitus Center, the Chair of the Center for Integrative Medicine for HFHS, Director of Product Development nutritional science projects ; for ViSalus Sciences, and a past President of the Michigan Otolaryngology Society. Additionally, he is an active scientist and has extramural funding from the National Institute of Health and other major institutions and desloratadine.

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BP P.L.C., the Registered Proprietor of Trade Mark No. 8062, has, by veritable proof tendered before the Registrar on the 16th day of June, 2005, being Certificate from the Registrar of Companies for England and Wales, executed at Companies House, Cardiff, on the 25th day of May, 2004, changed address from Britannic House, 1 Finsbury Circus, London EC2M 7BA, England, to 1 St James's Square, London SW1Y 4PD, England, as of the 25th day of May, 2004, the appropriate recordals of which have been effected in the Register. DATED this 20th day of June, 2005. NOTICE OF CHANGE OF ADDRESS OF PROPRIETOR and serophene.

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Harries AD, Maher D. TB HIV: a clinical manual. Geneva, World Health Organization, 1996 document WHO TB 96.200 ; . Treatment of tuberculosis: guidelines for national programmes, 2nd ed. Geneva, World Health Organization, 1997 document WHO TB 97.220 ; . Tuberculosis control in refugee situations: an inter-agency field manual. Geneva, World Health Organization, 1997 document WHO TB 97.221. Although there is evidence of some cross-resistance between amprenavir and the other protease inhibitors, there is also evidence that the I50V mutation is unique to amprenavir. Consequently, people with resistance to the established protease inhibitors may benefit from the use of amprenavir in salvage regimens. However, I50V compromises response to lopinavir. One study found that the number of protease inhibitors previously taken, and the duration of protease inhibitor treatment, did not predict phenotypic resistance to amprenavir. Instead, the I84 mutation and a naturally occurring variation, I93L, were associated with amprenavir resistance. However, another study reported that children with multiple resistance secondary mutations associated with the L90M mutation often responded poorly to amprenavir-based treatment. In contrast, the D30N mutation associated with resistance to nelfinavir Viracept ; did not reduce the effectiveness of amprenavir. Furthermore, the N88S protease mutation has been and clomiphene. 89. Wisner KL, Perel JM. Serum nortriptyline levels in nursing mothers and their infants. J Psychiatry. 1991; 148: 1234 Wisner KL, Perel JM. Nortriptyline treatment of breast-feeding women. J Psychiatry. 1996; 153: 295 Stowe ZN, Cohen LS, Hostetter A, Ritchie JC, Owens MJ, Nemeroff CB. Paroxetine in human breast milk and nursing infants. J Psychiatry. 2000; 157: 185189 Epperson CN, Anderson GM, McDougle CJ. Sertraline and breastfeeding. N Engl J Med. 1997; 336: 1189 Stowe ZN, Owens MJ, Landry JC, et al. Sertraline and desmethylsertraline in human breast milk and nursing infants. J Psychiatry. 1997; 154: 12551260 Verbeeck RK, Ross SG, McKenna EA. Excretion of trazodone in breast milk. Br J Clin Pharmacol. 1986; 22: 367370 Polishuk WZ, Kulcsar SA. Effects of chlorpromazine on pituitary function. J Clin Endocrinol Metab. 1956; 16: 292 Wiles DH, Orr MW, Kolakowska T. Chlorpromazine levels in plasma and milk of nursing mothers. Br J Clin Pharmacol. 1978; 5: 272273 Nielsen ST, Matheson I, Rasmussen JN, Skinnemoen K, Andrew E, Hafsahl G. Excretion of iohexol and metrizoate in human breast milk. Acta Radiol. 1987; 28: 523526 Ohkubo T, Shimoyama R, Sugawara K. Determination of chlorpromazine in human breast milk and serum by high-performance liquid chromatography. J Chromatogr. 1993; 614: 328 Matheson I, Evang A, Overo KF, Syversen G. Presence of chlorprothixene and its metabolites in breast milk. Eur J Clin Pharmacol. 1984; 27: 611 Barnas C, Bergant A, Hummer M, Saria A, Fleischhacker WW. Clozapine concentrations in maternal and fetal plasma, amniotic fluid, and breast milk. J Psychiatry. 1994; 151: 945 Stewart RB, Karas B, Springer PK. Haloperidol excretion in human milk. J Psychiatry. 1980; 137: 849 Whalley LJ, Blain PG, Prime JK. Haloperidol secreted in breast milk. Br Med J Clin Res Ed ; . 1981; 282: 1746 Ohkubo T, Shimoyama R, Sugawara K. Measurement of haloperidol in human breast milk by high-performance liquid chromatography. J Pharm Sci. 1992; 81: 947949 Yoshida K, Smith B, Craggs M, Kumar RC. Neuroleptic drugs in breast milk: a study of pharmacokinetics and of possible adverse effects in breast-fed infants. Psychol Med. 1998; 28: 8191 Ananth J. Side effects in the neonate from psychotropic agents excreted through breast-feeding. J Psychiatry. 1978; 135: 801 Plomp TA, Vulsma T, de Vijlder JJ. Use of amiodarone during pregnancy. Eur J Obstet Gynecol Reprod Biol. 1992; 43: 201207 Havelka J, Hejzlar M, Popov V, Viktorinova D, Prochazka J. Excretion of chloramphenicol in human milk. Chemotherapy. 1968; 13: 204 Smadel JE, Woodward TE, Ley HL Jr, et al. Chloramphenicol Chloromhcetin ; in the treatment of tsutsugamushi disease scrub typhus ; . J Clin Invest. 1949; 28: 1196 Venkatesan K, Mathur A, Girdhar A, Girdhar BK. Excretion of clofazimine in human milk in leprosy patients. Lepr Rev. 1997; 68: 242246 Tomson T, Ohman I, Vitols S. Lamotrigine in pregnancy and lactation: a case report. Epilepsia. 1997; 38: 1039 Gupta AP, Gupta PK. Metoclopramide as a lactogogue. Clin Pediatr Phila ; . 1985; 24: 269 Kauppila A, Arvela P, Koivisto M, Kivinen S, Ylikorkala O, Pelkonen O. Metoclopramide and breast feeding: transfer into milk and the newborn. Eur J Clin Pharmacol. 1983; 25: 819 Erickson SH, Oppenheim GL, Smith GH. Metronidazole in breast milk. Obstet Gynecol. 1981; 57: 48 Heisterberg L, Branebjerg PE. Blood and milk concentrations of metronidazole in mothers and infants. J Perinat Med. 1983; 11: 114 Evaldson GR, Lindgren S, Nord CE, Rane AT. Tinidazole milk excretion and pharmacokinetics in lactating women. Br J Clin Pharmacol. 1985; 19: 503507 Boutroy MJ, Bianchetti G, Dubruc C, Vert P, Morselli PL. To nurse when receiving acebutolol: is it dangerous for the neonate? Eur J Clin Pharmacol. 1986; 30: 737739 Nelis GF. Diarrhoea due to 5-aminosalicylic acid in breast milk. Lancet. 1989; 1: 383 Jenss H, Weber P, Hartmann F. 5-Aminosalicylic acid its metabolite in breast milk during lactation [letter]. J Gastroenterol. 1990; 85: 331 Klotz U, Harings-Kaim A. Negligible excretion of 5-aminosalicylic acid in breast milk. Lancet. 1993; 342: 618 Liedholm H, Melander A, Bitzen PO, et al. Accumulation of atenolol and metoprolol in human breast milk. Eur J Clin Pharmacol. 1981; 20: 229 Schimmel MS, Eidelman AI, Wilschanski MA, Shaw D Jr, Ogilvie RJ.

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Publishers for use of extensive quotations more than words ; . The Journal does not publish tables or figures have appeared in another English-language publication. Disclosure of Commercial Interests.

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