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Metabolism and Pharmacokinetics of Selective Serotonin Reuptake Inhibitors

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Abstract

1. Five drugs with the predominant pharmacologic effect of inhibiting the neuronal reuptake of serotonin are available worldwide for clinical use. This class of psychoactive drugs, known as selective serotonin reuptake inhibitors (SSRIs), is comprised of fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram.

2. The SSRIs appear to share similar pharmacodynamic properties which translate to efficacy in the treatment of depression and anxiety syndromes. The drugs are differentiated by their pharmacokinetic properties with regard to stereochemistry, metabolism, inhibition of cytochrome enzymes, and participation in drug–drug interactions. Studies focusing on the relationship of plasma drug concentration to therapeutic and adverse effects have not confirmed the value of plasma concentration monitoring.

3. This review summarizes the metabolism and relevant pharmacokinetic properties of the SSRIs.

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REFERENCES

  • Altamura, A. C., Moro, A. R., and Percudani (1994). Clinical pharmacokinetics of fluoxetine. Clin. Pharmacokinet. 26:201–214.

    Google Scholar 

  • Altshuler, L. L., Burt, V. K., McMullen, M., and Hendrick, V. (1995). Breastfeeding and sertraline: a 24-hour analysis. J. Clin. Psychiatry 56:243–245.

    Google Scholar 

  • Aronoff, G. R., Bergstrom, R. F., Pottratz, S. T., Sloan, R. S., Wolen, R. L., and Lemberger, L. (1984). Fluoxetine kinetics and protein binding in normal and impaired renal function. Clin. Pharmacol. Ther. 36:138–144.

    Google Scholar 

  • Baumann, P. (1992). Clinical pharmacokinetics of citalopram and other selective serotonergic III reuptake inhibitors. Int. Clin. Psychopharmacol. 6(Suppl. 5):13–20.

    Google Scholar 

  • Baumann, P. (1996). Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors. Clin. Pharmacokinet. 31:444–469.

    Google Scholar 

  • Baumann, P., Nil, R., Souche, A., Montaldi, S., Baettig, D., Lambert, S., Uehlinger, C., Kasas, A., Amey, M., and Jonzier-Perey, M. (1996). A double-blind placebo-controlled study of citalopram with and without lithium in the treatment of therapy-resistant depressive patients: A clinical pharmacokinetic, and pharmacogenetic investigation. J. Clin. Psychopharmacol. 16:307–314.

    Google Scholar 

  • Bealsey, C. M., Jr., Bosomworth, J. C., and Wernicke, J. F. (1990). Fluoxetine: Relationships among dose, response, adverse events, and plasma concentrations in the treatment of depression. Psychopharmacol. Bull. 26:18–24.

    Google Scholar 

  • Benfield, P., and Ward, A. (1986). Fluvoxamine: A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. Drugs 32:313–334.

    Google Scholar 

  • Bergstrom, R. F., van Lier, R. B. L., Lemberger, L., and Tenbarge, J. L. (1986). Absolute bioavailability of fluoxetine in beagle dogs. Abstr. Am. Pharm. Assoc. Acad. Pharm. Sci. 16:126.

    Google Scholar 

  • Bergstrom, R. F., Lemberger, L. Farid, N. A., and Wolen, R. L. (1988a). Clinical pharmacology and pharmacokinetics of fluoxetine: A review. Br. J. Psychiatry 153(Suppl. 3):47–50.

    Google Scholar 

  • Bergstrom, R. F., et al. (1988b). Relative bioequivalence of a fluoxetine oral solution versus the marketed capsule. Pharm. Res. 7(Suppl. 3):158.

    Google Scholar 

  • Bjerkenstedt, L., Flyckt, L., Fredrickson Overø, K., and Lingjaerde, O. (1985). Relationship between clinical effects, serum drug concentrations and serotonin uptake inhibition in depressed patients treated with citalopram. Eur. J. Clin. Pharmacol. 28:553–557.

    Google Scholar 

  • Bloomer, J. C., Woods, F. R., Haddock, R. E., Lennard, M. S., and Tucker, G. T. (1992). The role of cytochrome P4502D6 in the metabolism of paroxetine by human liver microsomes. Br. J. Clin. Pharmacol. 33:521–523.

    Google Scholar 

  • Brett, M. A., Dierdorf, H.-D., Zussman, B. D. and Coates, P. E. (1987). Determination of paroxetine in human plasma, using high-performance liquid chromatography with fluorescence detection. J. Chromatogr. B Appl. 419:438–444.

    Google Scholar 

  • Brosen, K., Skjelbo, E., Rasmussen, B. B., Poulsen, H. E., and Loft, S. (1993). Fluvoxamine is a potent inhibitor of cytochrome P450 1A2. Biochem. Pharmacol. 45:1211–1214.

    Google Scholar 

  • Caccia, S., Cappi, M., Francasso, C., and Garattini, S. (1990). Influence of dose and route of administration on the kinetics of fluoxetine and its metabolite norfluoxetine in the rat. Psychopharmacology 100: 509–514.

    Google Scholar 

  • Carrillo, J. A., Dahl, M.-L., Svensson, J.-O., Alm, C., Rodríguez, I., and Bertilsson, L. (1996). Disposition of fluvoxamine in humans is determined by the polymorphic CYP2D6 and also by the CYP1A2 activity. Clin. Pharmacol. Ther. 60:183–190.

    Google Scholar 

  • Ceccherini-Nelli Guidi, L. (1993). Fluoxetine: The relationship between response, adverse events, and plasma concentrations in the treatment of bulimia nervosa. Int. Clin. Psychopharmacol. 8:311–313.

    Google Scholar 

  • Classen, V. (1983). Review of the animal pharmacology and pharmacokinetics of fluvoxamine. Br. J. Clin. Pharmacol. 15(Suppl. 3):349S-355S

    Google Scholar 

  • Crewe, H. K., Lennard, M. S., Tucker, G. T., Woods, F. R., and Haddock, R. E. (1992). The effect of selective serotonin reuptake inhibitors on cytochrome P4502D6 activity in human liver microsomes. Br. J. Clin. Pharmacol. 45:1211–1214.

    Google Scholar 

  • Danish University Antidepressant Group (1990). Paroxetine: A selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect than clomipramine in a controlled multicenter study. J. Affect. Disord. 18:289–299.

    Google Scholar 

  • De Bree, H., van der Schoot, J. B., and Post, L. C. (1983). Fluvoxamine maleate: Disposition in man. Eur. J. Drug Metab. Pharmacokin. 8:175–179.

    Google Scholar 

  • Dechant, K. L., and Clissold, S. P. (1991). Paroxetine: A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness. Drugs 41:225–253.

    Google Scholar 

  • DeVane, C. L. (1994). Pharmacokinetics of the newer antidepressants: Clinical relevance. Am. J. Med. 97(Suppl. 6A):13–23.

    Google Scholar 

  • DeVane, C. L. (1997). The place of selective serotonin reuptake inhibitors in the treatment of panic disorder. Pharmacotherapy 17:282–292.

    Google Scholar 

  • DeVane, O. L., and Jusko, W. J. (1983). Drug and metabolite concentrations combined in predicting steady-state concentrations from test doses. Biopharm. Drug Disp. 4:19–29.

    Google Scholar 

  • de Vries, M. F., Raghoebar, M., Mathlener, J. S., and van Harten, J. (1992). Single and multiple oral dose fluvoxamine kinetics in young and elderly subjects. Ther. Drug Monit. 14:493–498.

    Google Scholar 

  • de Vries, M. H., van Harten, J., van Bemmel, P., and Raghoebar, M. (1993). Pharmacokinetics of fluvoxamine maleate after increasing single oral doses in healthy subjects. Biopharm. Drug Disp. 14:291–296.

    Google Scholar 

  • DeWilde, J. E. M., and Doogan, D. P. (1982). Fluvoxamine and chlorimipramine in endogenous depression. J. Affect. Dis. 4:249–259.

    Google Scholar 

  • DeWilde, J. E., Mertens, C., and Wakelin, J. S. (1983). Clinical trials of fluvoxamine vs. chlorimipramine with single and three times daily dosing. Br. J. Clin. Pharmacol. 15:427S-431S.

    Google Scholar 

  • Dixit, V., Nguyen, H., and Dixit, V. M. (1991). Solid-phase extraction of fluoxetine and norfluoxetine from serum with gas chromatography-electron-capture detection. J. Chromatogr. 563:379–384.

    Google Scholar 

  • Doyle, G. D., Lehar, M., Kelly, J. G., Byrne, M. M., and Clarkson, A. (1989). The pharmacokinetics of paroxetine in renal impairment. Acta Psychiatr. Scand. Suppl. 350:89–90.

    Google Scholar 

  • Eap, C. B., Gaillard, N., Powell, K., and Baumann, P. (1996). Simultaneous determination of plasma levels of fluvoxamine and of the enantiomers of fluoxetine and norfluoxetine by gas chromatographymass spectrometry. J. Chromatogr. Biomed. Appl. 682:265–272.

    Google Scholar 

  • Fava, M., Rosenbaum, J. R., Cohen, L., Reiter, S., McCarthy, M., Steingard, R., and Clancy, K. (1992). High-dose fluoxetine in the treatment of depressed patients not responsive to a standard dose of fluoxetine. J. Affect. Dis. 25:229–234.

    Google Scholar 

  • Foglia, J. P., Birder, L. A., and Perel, J. M. (1989). Determination of fluvoxamine in human plasma by high-performance liquid chromatography with ultraviolet detection. J. Chromatogr. 495:295–302.

    Google Scholar 

  • Foglia, J. P., Perel, J. M., Nathan, R. S., and Pollock, B. G. (1990). Therapeutic drug monitoring of fluvoxamine, a selective antidepressant. Clin. Chem. 36:1043 (abstract).

    Google Scholar 

  • Fouda, H. G., and Ronfeld, R. A. (1987). Gas chromatographic-mass spectrometric analysis and preliminary human pharmacokinetics of sertraline, a new antidepressant drug. J. Chromatogr. Biomed. Appl. 417:197–202.

    Google Scholar 

  • Fuller, R. W., Snoddy, H. D., Krushinski, J. H., and Robertson, D. W. (1992). Comparison of norfluoxetine enantiomers as serotonin uptake inhibitors in vivo. Neuropharmacology 31:997–1000.

    Google Scholar 

  • Fuller, R. W., Hemrick-Luecke, S. K., Litterfield, E. S., and Audia, J. E. (1995). Comparison of desmethylsertraline with sertraline as a monoamine uptake inhibitor in vivo. Life Sci. 19:135–149.

    Google Scholar 

  • Goodman, W. K., Price, L. H., Delgado, P. L., Palumbo, J., Krystal, J. H., Nagy, L. M., Rasmussen, S. A., Heninger, G. R., and Charney, D. S. (1990). Specificity of serotonin reuptake inhibitors in the treatment of obsessive compulsive disorder: Comparison of fluvoxamine and desipramine. Arch. Gen. Psychiatry 47:577–585.

    Google Scholar 

  • Goff, D. C., Midha, K. K., Sarid-Segal, O., Hubbard, J. W., and Amico, E. (1995). A placebo-controlled trial of fluoxetine added to neuroleptic in patients with schizophrenia. Psychopharmacology 117:417–423.

    Google Scholar 

  • Gram, L. F. (1994). Fluoxetine. N. Engl. J. Med. 331:1354–1361.

    Google Scholar 

  • Greenblatt, D. J., von Moltke, L. L., Schmider, J., Harmatz, J. S., and Shader, R. I. (1996). Inhibition of human cytochrome P450–3A isoforms by fluoxetine and norfluoxetine: In vitro and in vivo studies. J. Clin. Pharmacol. 36:792–798.

    Google Scholar 

  • Grimsley, S. R., and Jann, M. W. (1992). Paroxetine, sertraline, and fluvoxamine: New selective serotonin reuptake inhibitors. Clin. Pharm. 11:930–957.

    Google Scholar 

  • Gupta, R. N. (1994). Column liquid chromatographic determination of paroxetine in human serum using solid-phase extraction. J. Chromatogr. B Biomed. Appl. 661:362–365.

    Google Scholar 

  • Gupta, R. N., and Dziurdzy, S. A. (1994). Therapeutic monitoring of sertraline. Clin. Chem. 40:498–499.

    Google Scholar 

  • Gupta, R. N., and Steiner, M. (1990). Determination of fluoxetine and norfluoxetine in serum by liquid chromatography with fluorescence detection. J. Liquid Chromatogr. 13:3785–3797.

    Google Scholar 

  • Haddock, R. E., Johnson, A. M., Langley, P. F., Nelson, D. R., Pope, J. A., Thomas, D. R., and Woods, F. R. (1989). Metabolic pathway of paroxetine in animals and man and the comparative pharmacological properties of its metabolites. Acta Psychiatr. Scand. 80(Suppl. 350):24–26.

    Google Scholar 

  • Hamelin, B. A., Turgeon, J., Vallee, F., Belanger, P.-M., Paquet, F., and LeBel, M. (1996). Role of CYP2D6 in the demethylation of fluoxetine in vivo. Clin. Pharmacol. Ther. 59:137.

    Google Scholar 

  • Hartter, S., Wetzel, H., and Hiemke, C. (1992). Automated determination of fluvoxamine in human plasma by column switching high-performance liquid chromatography. Clin. Chem. 38:2082–2086.

    Google Scholar 

  • Hartter, S., Hermes, B., Szegedi, A., and Hiemke, C. (1994). Automated determination of paroxetine and its main metabolite by column switching and on-line high-performance liquid chromatography. Ther. Drug Monit. 16:400–406.

    Google Scholar 

  • Harvey, A. T., and Preskorn, S. H. (1996). Cytochrome P450 enzymes: Interpretation of their interactions with selective serotonin reuptake inhibitors. J. Clin. Psychopharmacol. 16:273–285.

    Google Scholar 

  • Hurst, H. E., Jones, D. R., Jarboe, C. H., and deBree, H. (1981). Determination of clovoxamine concentration in human plasma by electron capture gas chromatography. Clin. Chem. 27:1210–1212.

    Google Scholar 

  • Hyttel, J., Bogeso, K. P., Perregaard, J., and Sanchez, C. (1992). The pharmacological effect of citalopram resides in the (S)-(+)-enantiomer. J. Neural Transm. 88:157–160.

    Google Scholar 

  • Isenberg, K. E. (1990). Excretion of fluoxetine in human breast milk. J. Clin. Psychiatry 51:169.

    Google Scholar 

  • Kasper, S., Dotsch, M., and Vieira, A. (1992). Plasma levels of fluvoxamine and maprotiline and clinical response in major depression. Pharmacopsychiatry 25:106.

    Google Scholar 

  • Kasper, S., Dotsch, M., Kick, H., Vieira, A., and Möller, H.-J. (1993). Plasma concentrations of fluvoxamine and maprotiline in major depression: Implications of therapeutic efficacy and side effects. Eur. Neuropsychopharmacol. 3:13–21.

    Google Scholar 

  • Kaye, C. M., Haddock, R. E., Langley, P. F., Mellows, G., Tasker, T. C. G., Zussman, B. D., and Greb, W. H. (1989). A review of the metabolism and pharmacokinetics of paroxetine in man. Acta Psychiatr. Scand. 80(Suppl. 350):60–75.

    Google Scholar 

  • Keck, P. E., Jr., and McElroy, S. L. (1992). Ratio of plasma fluoxetine to norfluoxetine concentrations and associated sedation. J. Clin. Psychiatry 53:127–129.

    Google Scholar 

  • Kelly, M. W., Perry, P. J., Holstad, S. G., and Garvey, M. J. (1989). Serum fluoxetine and norfluoxetine concentrations and antidepressant response. Ther. Drug Monitor. 11:163–170.

    Google Scholar 

  • Keogh, A., Spratt, P., McCosker, C., MacDonald, P., Mundy, J., and Kaan, A. (1995). Ketoconazole to reduce the need for cyclosporine after cardiac transplantation. N. Engl. J. Med. 333:628–633.

    Google Scholar 

  • Ketter, T. A., Callahan, A. M., and Post, R. (1996). Nefazodone relief of alprazolam interdose dysphoria: A potential therapeutic benefit of 3A3/4 inhibition. J. Clin. Psychiatry 57:307.

    Google Scholar 

  • Klok, C. J., Brouwer, G. J., VanPraag, H. M., and Doogan, D. (1981). Fluvoxamine and clomipramine in depressed patients. Acta Psychiatr. Scand. 64:1–11.

    Google Scholar 

  • Kobayashi, K., Yamamoto, T., Chiba, K., Tani, M., Ishizaki, T., and Kuroiwa, Y. (1995). The effects of selective serotonin reuptake inhibitors and their metabolites on S-mephenytoin 4′-hydroxylase activity in human liver microsomes. Br. J. Clin. Pharmacol. 40:481–485.

    Google Scholar 

  • Koe, B. K., Weissman, A., Welch, W. M., and Browne, R. G. (1983). Sertraline, 1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthylamine, a new uptake inhibitor with selectivity for serotonin. J. Pharmacol. Exp. Ther. 226:686–700.

    Google Scholar 

  • Kragh-Sørensen, P., Overø, K. F., Petersen, O. L., Jensen, K., and Parnas, W. (1981). The kinetics of citalopram: Single and multiple dose studies in man. Acta Pharmacol. Toxicol. 48:53–60.

    Google Scholar 

  • Krastev, Z., Terziivanov, D., Vlahov, V., Maleev, A., and Greb, W. H. (1989). The pharmacokinetics of paroxetine in patients with liver cirrhosis. Acta Psychiatr. Scand. 80(Suppl. 350):91–92.

    Google Scholar 

  • Kuhs, H., Schlake, H.-P., Rolf, L. H., and Rudolf, G. A. E. (1992). Relationship between parameters of serotonin transport and antidepressant plasma levels or therapeutic response in depressive patients treated with paroxetine and amitriptyline. Acta Psychiatr. Scand. 85:364–369.

    Google Scholar 

  • Lane, R. M. (1996). Pharmacokinetic drug interaction potential of selective serotonin reuptake inhibitors. Int. Clin. Psychopharmacol. 11(Suppl. 5):31–61.

    Google Scholar 

  • Lantz, R. J., Farid, K. Z., Koons, J., Tenbarge, J. B., and Bopp, R. J. (1991). Determination of fluoxetine and norfluoxetine in human plasma by capillary gas chromatography with electron-capture detection. J. Chromatogr. B Biomed. Appl. 563:379–384.

    Google Scholar 

  • Leinonen, E., Lepola, U., Koponen, H., and Kinnunen, I. (1996). The effect of age and concurrent treatment with other psychoactive drugs on serum concentration of citalopram measured with a nonenantioselective method. Ther. Drug Monit. 18:111–117.

    Google Scholar 

  • Lester, B. M., Cucca, J., Andreozzi, L., Flanagan, P., and Oh, W. (1993). Possible association between fluoxetine hydrochloride and colic in an infant. J. Am. Acad. Child Adolesc. Psychiatry 32:1253–1255.

    Google Scholar 

  • Lund Laursen, A., Mikkelsen, P. L., Rasmussen, S., and le Fèvre Honorè, P. (1985). Paroxetine in the treatment of depression: A randomized comparison with amitriptyline. Acta Psychiatr. Scand. 71: 249–255.

    Google Scholar 

  • Luvox Product Information (1994). Solvey Pharmaceuticals, Inc.

  • Martensson, B., Nyberg, S., Toresson, G., Brodin, E., and Bertilsson, L. (1989). Fluoxetine treatment of depression. Acta Psychiatr. Scand. 79:586–596.

    Google Scholar 

  • Matsui, E., Hoshino, M., Matsui, A., and Okahira, A. (1995). Simultaneous determination of citalopram and its metabolites by high performance liquid chromatography with column switching and fluorescence detection by direct plasma injection. J. Chromatogr. 668:299–307.

    Google Scholar 

  • Milne, R. J., and Goa, K. L. (1991). Citalopram. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in depressive illness. Drugs 41:450–477.

    Google Scholar 

  • Montgomery, S. A., Baldwin, D., Shah, A., Green, M., Fineberg, N., and Montgomery, D. (1990). Plasma level response relationships with fluoxetine and zimelidine. Clin. Neuropharmacol. 13(Suppl. 1):S71-S73.

    Google Scholar 

  • Nelson, J. C., Mazure, C. M., Bowers, M. B., Jr., and Jatlow, P. I. (1991). A preliminary, open study of the combination of fluoxetine and desipramine for rapid treatment of major depression. Arch. Gen. Psychiatry 48:303–307.

    Google Scholar 

  • Nemeroff, C. B., DeVane, C. L., and Pollock, B. G. (1996). Antidepressants and the cytochrome P450 system. Am. J. Psychiatry 143:311–320.

    Google Scholar 

  • Norman, R. T., Gupta, R. K., Burrows, G. D., Parker, G., and Judd, F. K. (1993). Relationship between antidepressant response and plasma concentrations of fluoxetine and norfluoxetine. Int. Clin. Psychopharmacol. 8:25–29.

    Google Scholar 

  • Orsulak, P. J., Denny, J. P., Debus, J. R., Crowley, G., and Wittman, P. D. (1988). Determination of the antidepressant fluoxetine and its metabolite norfluoxetine in serum by reversed-phase HPLC, with ultraviolet detection. Clin. Chem. 34:1875.

    Google Scholar 

  • Overmars, H., Scherpenisse, P. M., and Post, L. C. (1983). Fluvoxamine maleate: metabolism in man. Eur. J. Drug Metab. Pharmacokinet. 8:269–280.

    Google Scholar 

  • Overø, K. F. (1978). Preliminary studies of the kinetics of citalopram in man. Eur. J. Clin. Pharmacol. 14:69–73.

    Google Scholar 

  • Overø, K. F. (1982). Kinetics of citalopram in man: Plasma levels in patients. Prog. Neuropsychopharmacol. Biol. Psychiatry 6:311–318.

    Google Scholar 

  • Overø, K. F., Toft, B., Christophersen, L., and Gylding-Sabroe, J. P. (1985). Kinetics of citalopram in elderly patients. Psychopharmacology 86:253–257.

    Google Scholar 

  • Parli, C. J., and Hicks, J. (1974). In vivo demethylation of Lilly 110140: 3-(p-Rifluoromethylphenoxy)-N-methyl-3-phenylpropylamine to an active metabolite-Lilly 103947. Fed. Proc. 33:560.

    Google Scholar 

  • Perucca, E., Gatti, G., and Spina, E. (1994). Clinical pharmacokinetics of fluvoxamine. Clin. Pharmacokinet. 27:175–190.

    Google Scholar 

  • Peterson, E. N., Bechgaard, E., Sortwell, R. J., and Wetterberg, L. (1978). Potent depletion of 5HT from monkey whole blood by a new 5HT uptake inhibitor, paroxetine. Eur. J. Pharmacol. 52:115–119.

    Google Scholar 

  • Peyton, A. L., Carpenter, R., and Rutkowski, K. (1991). The stereospecific determination of fluoxetine and norfluoxetine enantiomers in human plasma by high-pressure liquid chromatography with fluorescence detection. Pharm. Res. 8:1528–1532.

    Google Scholar 

  • Potts, B. D., and Parli, C. J. (1992). Analysis of the enantiomers of fluoxetine and norfluoxetine in plasma and tissue using chiral derivatization and normal-phase liquid chromatography. J. Liq. Chromatogr. 15:665–681.

    Google Scholar 

  • Raymond, P., Amey, M., Soncle, A., Lambert, S., Konrat, H., Eap, C. B., and Baumann, P. (1993). Determination of plasma levels of citalopram and its demethylated and deaminated metabolities by gas chromatography-mass spectrometry. J. Chromatogr. 616:221–228.

    Google Scholar 

  • Rochat, B., Amey, M., Van Gelderen, H., Testa, B., and Baumann, P. (1995). Determination of the enantiomers of citalopram, its demethylated and propionic acid metabolites in human plasma by chiral HPLC. Chirality 7:389–395.

    Google Scholar 

  • Rogowsky, D., Marr, M., Long, G., and Moore, C. (1994). Determination of sertraline and desmethylsertraline in human serum using copolymeric bonded-phase extraction, liquid chromatography and gas chromatography-mass spectrometry. J. Chromatogr. BioAppl. 655:138–141.

    Google Scholar 

  • Ronfeld, R. A., Shaw, G. L., and Tremaine, L. M. (1988). Distribution and pharmacokinetics of the selective 5-HT uptake blockers sertraline in man, rat and dog. Psychopharmacology 96(Suppl.): 269 (abstract).

    Google Scholar 

  • Ruijten, H. M., De Bree, H., Borst, A. J. M., De Lange, N., Scherpenisse, P. M., Vincent, W. R., and Post, L. C. (1984). Fluvoxamine: Metabolic fate in animals. Drug Metab. Disp. 12:82–92.

    Google Scholar 

  • Saletu, B., Grunberger, J., and Linzmayer, L. (1986). On central effects of serotonin re-uptake inhibitors: Quantitative EEG and psychometric studies with sertraline and zimelidine. J. Neural Transm. 67:241–266.

    Google Scholar 

  • Schenker, S., Bergstrom, R. F., Wolen, R. L., and Lemberger, L. (1988). Fluoxetine disposition and elimination in cirrhosis. Clin. Pharmacol. Ther. 44:353–359.

    Google Scholar 

  • Schweitzer, C., Spahn, H., and Mutschler, E. (1986). Fluorimetric determination of fluvoxamine or clovoxamine in human plasma after thin-layer chromatographic or high-performance liquid chromatographic separation. J. Chromatogr. 382:405–411.

    Google Scholar 

  • Sindrup, S. H., Brøsen, K., Gram, L. F., Hallas, J., Skjelbo, E., Allen, A., Allen, G. D., Cooper, S. M., Mellows, G., Tasker, T. C. G., and Zussman, B. D. (1992a). The relationship between paroxetine and the sparteine oxidation polymorphism. Clin. Pharmacol. Ther. 51:278–287.

    Google Scholar 

  • Sindrup, S. H., Brøsen, K., and Gram, L. F. (1992b). Pharmacokinetics of the selective serotonin reuptake inhibitor paroxetine: Nonlinearity and relation to the sparteine oxidation polymorphism. Clin. Pharmacol. Ther. 51:288–195.

    Google Scholar 

  • Sindrup, S. H., Brøsen, K., Hansen, M. G. J., Aaes-Jørgensen, T., Overø, K. F., and Gram, L. F. (1993). Pharmacokinetics of citalopram in relation to the sparteine and the mephenytoin oxidation polymorphisms. Ther. Drug Monitor. 15:11–17.

    Google Scholar 

  • Skjelbo, E., and Brøsen, K. (1992). Inhibitors of imipramine metabolism by human liver microsomes. Br. J. Clin. Pharmacol. 34:256–261.

    Google Scholar 

  • Spigset, O., Carleborg, L., Hedenmalm, K., and Dahlqvist, R. (1995). Effect of cigarette smoking on fluvoxamine pharmacokinetics in humans. Clin. Pharmacol. Ther. 58:399–403.

    Google Scholar 

  • Stevens, J. C., and Wrighton, S. A. (1993). Interaction of the enantiomers of fluoxetine and norfluoxetine with human liver cytochromes P450. J. Pharmacol. Exp. Ther. 226:964–971.

    Google Scholar 

  • Szegedi, A., Wiesner, J., and Hiemke, C. (1995). Improved efficacy and fewer side effects under clozapine treatment after addition of fluvoxamine. J. Clin. Psychopharmacol. 15:141–143.

    Google Scholar 

  • Tasker, T. C. G., Kaye, C. M., Zussman, B. D., and Link, C. G. G. (1989). Paroxetine plasma levels: Lack of correlation with efficacy or adverse events. Acta Psychiatr. Scand. 80(Suppl. 350):152–155.

    Google Scholar 

  • Torok-Both, G. A., Baker, G. B., Coutts, R. T., McKenna, K. F., and Aspeslet, L. J. (1992). Simultaneous determination of fluoxetine and norfluoxetine enantiomers in biological samples by gas chromatography with electron-capture detection. J. Chromatogr. B Biomed. Appl. 579:99–106.

    Google Scholar 

  • Tremaine, L. M., and Joerg, E. A. (1989). Automated gas chromatographic-electron capture assay for the selective serotonin uptake blocker sertraline. J. Chromatogr. 496:423–429.

    Google Scholar 

  • Tremaine, L. M., Welch, W. M., and Ronfeld, R. A. (1989). Metabolism and disposition of the 5-hydroxytryptamine uptake blocker sertraline in the rat and dog. Drug Metab. Disp. 17:542–550.

    Google Scholar 

  • Tyrer, S. P., Marshall, E. F., and Griffiths, H. W. (1990). The relationship between response to fluoxetine, plasma drug levels, imipramine biding to platelet membranes and whole blood 5-HT. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 14:797–805.

    Google Scholar 

  • Van der Meersch-Mougeot, V., and Diquet, B. (1991). Sensitive one-step extraction procedure for column liquid chromatographic determination of fluvoxamine in human and rat plasma. J. Chromatogr. 567:441–449.

    Google Scholar 

  • Van Harten, J., Van Bemmel, P., Dobrinska, M. R., Ferguson, R. K., and Raghoebar, M. (1991). Bioavailability of fluvoxamine given with and without food. Biopharm. Drug Disp. 12:571–575.

    Google Scholar 

  • Van Harten, J., Duchier, J., Devissaguet, J.-P., van Bemmel, P., de Vries, M. H. and Raghoebar, M. (1993). Pharmacokinetics of fluvoxamine maleate in patients with liver cirrhosis after single-dose administration. Clin. Pharmacokinet.7 24:177–182.

    Google Scholar 

  • von Moltke, L. L., Greenblatt, D. J., Cotreau-Bibbo, M. M., Duan, S. X., Harmatz, J. S., and Shader, R. I. (1994). Inhibition of desipramine hydroxylation in vitro by serotonin-reuptake-inhibitor antidepressants, and by quinidine and ketoconazole: A model system to predict drug interactions in vivo. J. Pharmacol. Exp. Ther. 268:1278–1283.

    Google Scholar 

  • von Moltke, L. L., Greenblatt, D. J., Court, M. H., Duan, S. X., Harmatz, J. S., and Shader, R. I. (1995). Inhibition of alprazolam and desipramine hydroxylation in vitro by paroxetine and fluvoxamine: Comparison with other selective serotonin reuptake inhibitor antidepressants. J. Clin. Psychopharmacol. 15:125–131.

    Google Scholar 

  • Warrington, S. J. (1992). Clinical implications of the pharmacology of sertraline. Int. Clin. Psychopharmacol. 6(Suppl. 2):11–21.

    Google Scholar 

  • Wiener, H. L., Kramer, H. K., and Reith, M. E. A. (1990). Separation and determination of sertraline and its metabolite, desmethylsertraline, in mouse cerebral cortex by reversed-phase high-performance liquid chromatography. J. Chromatogr. Biomed. Appl. 527:467–472.

    Google Scholar 

  • Wong, S. H. Y., Dellafera, S. S., Fernandes, R., and Kranzler, H. (1990a). Determination of fluoxetine and norfluoxetine by high performance liquid chromatography. J. Chromatogr. 499:601.

    Google Scholar 

  • Wong, D. T., Fuller, R. W., and Robertson, D. W. (1990b). Fluoxetine and its two enantiomers as selective serotonin uptake inhibitors. Acta Pharm. Nord. 2:171–180.

    Google Scholar 

  • Wright, S., Dawling, S., and Ashford, J. J. (1991). Excretion of fluvoxamine in breast milk. Br. J. Clin. Pharmacol. 31:209.

    Google Scholar 

  • Zoloft Prescribing Information (1996). Pfizer Pharmaceuticals, Inc.

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  1. Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, 29425

    C. Lindsay DeVane

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DeVane, C.L. Metabolism and Pharmacokinetics of Selective Serotonin Reuptake Inhibitors. Cell Mol Neurobiol 19, 443–466 (1999). https://doi.org/10.1023/A:1006934807375

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