Metabolism of the newer antidepressants: An overview of the pharmacological and pharmacokinetic implications

Clinical Pharmacokinetics

Volumn 34, Issue 4, 1998, Pages 281-302

  Caccia, Silvio ^a  

^a MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIDEPRESSANT AGENT; CYTOCHROME P450; DRUG METABOLITE; FLUOXETINE; FLUVOXAMINE; ISOENZYME; MILNACIPRAN; MIRTAZAPINE; MOCLOBEMIDE; NEFAZODONE; REBOXETINE; SEROTONIN UPTAKE INHIBITOR; TIANEPTINE; VENLAFAXINE;

BLOOD BRAIN BARRIER; CHIRALITY; DRUG CLEARANCE; DRUG METABOLISM; DRUG POTENCY; DRUG TRANSFORMATION; DRUG URINE LEVEL; GENETIC POLYMORPHISM; OXIDATION; PRIORITY JOURNAL; REVIEW; STEREOISOMERISM;

ADRENERGIC ALPHA-ANTAGONISTS; ADRENERGIC UPTAKE INHIBITORS; ANIMALS; ANTIDEPRESSIVE AGENTS; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; ISOENZYMES; MONOAMINE OXIDASE INHIBITORS; SEROTONIN ANTAGONISTS; SEROTONIN UPTAKE INHIBITORS;

EID: 0031979755     PISSN: 03125963     EISSN: None     Source Type: Journal    
DOI: 10.2165/00003088-199834040-00002     Document Type: Review

References (157)

1. Coccaro EF, Siever LJ. Second generation antidepressants: a comparative review. J Clin Pharmacol 1985; 25: 241-60
2. Blackwell B, Simon JS. Second-generation antidepressants. Drugs Today 1986; 22: 611-33
3. Hollister LH. Current antidepressants. Annu Rev Pharmacol Toxicol 1993; 26: 23-37
4. Rudorfer MV, Potter WZ. Antidepressants: a comparative review of the clinical pharmacology and therapeutic use of the 'newer' versus the 'older' drugs. Drugs 1989; 37: 713-38
5. Möller H-J, Volz H-P. Drug treatment of depression in the 1990s: an overview of achievements and future possibilities. Drugs 1996; 52: 625-6
6. Skerritt U, Evans R, Montgomery SA. Selective serotonin reuptake inhibits in older patients: a tolerability perspective. Drugs Aging 1997; 10: 209-18
7. Amsterdam J, Brunswick D, Mendels J. The clinical application of tricyclic antidepressant pharmacokinetics and plasma levels. Am J Psychiatry 1980; 137: 653-62
8. Guthrie S, Lane HA, Linnoila M. Monitoring of plasma drug concentrations in clinical psychopharmacology. In: Meltzer HY, editor. Psychopharmacology: the third generation of progress. New York: Raven Press, 1987: 1323-9
9. Preskorn SH, Dorey RC, Jerkovich GS. Therapeutic drug monitoring of tricyclic antidepressants. Clin Chem 1988; 34: 822-8
10. Orsulak PJ. Therapeutic monitoring of antidepressant drugs: guidelines updated. Ther Drug Monit 1989; 11: 497-507
11. Caccia S, Garattini S, Formation of active metabolites of psychotropic drugs: an updated review of their significance. Clin Pharmacokinet 1990; 18: 434-59
12. Potter WZ, Manji HK. Antidepressants, metabolites, and apparent drug resistance. Clin Neuropharmacol 1990; 13 Suppl. 1: S45-53
13. Nordin C, Bertilsson L. Active hydroxymetabolites of antidepressants: emphasis on E-10-hydroxy-nortriptyline. Clin Pharmacokinet 1995; 28: 26-40
14. Caccia S, Garattini S. Pharmacokinetic and pharmacodynamic significance of antidepressant drug metabolites. Pharmacol Res 1992; 26: 317-29
15. Preskorn SH. Pharmacokinetics of antidepressants: why and how they are relevant to treatment. J Clin Psychiatry 1993; 54 Suppl.: 14-34
16. DeVane CL. Pharmacokinetics of the newer antidepressants: Clinical relevance. Am J Med 1994; 97 Suppl. 6A: 13S-23S
17. Goodnick PJ. Pharmacokinetic optimisation of therapy with newer antidepressants. Clin Pharmacokinet 1994; 27: 307-30
18. Baumann P. Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors. Clin Pharmacokinet 1996; 31: 444-69
19. Rudorfer MV, Potter WZ. The role of metabolites of antidepressants in the treatment of depression. CNS Drugs 1997; 7: 273-312
20. Claassen V. Review of the animal pharmacology and pharmacokinetics of fluvoxamine. Br J Clin Pharmacol 1983; 15: 349S-55S
21. Dechant KL, Clissold SP. Paroxetine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness. Drugs 1991; 41: 225-53
22. Milne CJ, Goa KL. Citalopram: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness. Drugs 1991; 41: 450-77
23. Benfield P, Heel RC, Lewis SP. Fluoxetine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. Drugs 1986; 32: 481-508
24. Wong DT, Bymaster FP, Held LR, et al. Norfluoxetine enantiomers as inhibitors of serotonin uptake in rat brain. Neuropsychopharmacology 1993; 8: 337-44
25. Fuller, RW. Wong DT. Serotonin re-uptake blockers in vitro and in vivo. J Clin Psychopharmacol 1987; 7: 365-435
26. Murdoch D, McTavish D. Sertraline: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depression and obsessive-compulsive disorder. Drugs 1992; 44: 604-24
27. Ronfeld RA, Tremaine LM, Wilner KD. Pharmacokinetics of sertraline and its N-demethyl metabolite in elderly and young male and female volunteers. Clin Pharmacokinet 1997; 32: Suppl. 1: 22-30
28. Benfield P, Ward A. Fluvoxamine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. Drugs 1986; 32: 313-34
29. Preskorn SH, Magnus RD. Inhibition of hepatic P-450 isoenzymes by serotonin selective reuptake inhibitors: in vitro and in vivo findings and their implications for patient care. Psychopharmacol Bull 1994; 30: 251-9
30. Lane RM. Pharmacokinetic drug interaction potential of selective serotonin reuptake inhibitors. Int Clin Psychopharmacol 1996; 11 Suppl. 5: 31-61
31. Nemeroff CB, DeVane CL, Pollock BG. Newer antidepressants and the cytochrome P450 system. Am J Psychiatry 1996; 153: 311-20
32. Beequemont L, Ragueneau I, Le Bot MA, et al. Influence of the CYPIA2 inhibitor fluvoxamine on tacrine pharmacokinetics in humans. Clin Pharmacol Ther 1997; 61: 619-27
33. Spigset O, Carleborg L, Hedenmalm K, et al. Effect of cigarette smoking on fluvoxamine pharmacokinetics in humans. Clin Pharmacol Ther 1995; 58: 399-403
34. Crewe HK, Lennard MS, Tucker GT, et al. The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes. Br J Clin Pharmacol 1992; 34: 262-5
35. Skjelbo L, Brosen K. Inhibitors of imipramine metabolism by human liver microsomes. Br J Clin Pharmacol 1992; 34: 256-61
36. von Moltke LL, Greenblutt DJ, Court MH, et al. Inhibition of alprazolam and desipramine hydroxylation by paroxetine and fluvoxamine: comparison with other selective serotonin reuptake inhibitor antidepressants. J Clin Psychopharmacol 1995; 15: 125-31
37. Jeppesen L, Rasmussen BB, Brosen K. Fluvoxamine inhibits the CYP2C19-catalyzed bioactivation of chloroguanide. Clin Pharmacol Ther 1997; 62: 279-86
38. Hartter S, Wetzel H, Hammes E, et al. Inhibition of antidepressant demethylation and hydroxylation by fluvoxamine in depressed patients. Psychopharmacology 1993; 110: 302-8
39. Kaye CM, Haddock RE, Langley PF, et al. A review of the metabolism and pharmacokinetics of paroxetine in man. Acta Psychiatr Scand 1989; 80 Suppl. 350: 60-75
40. Crewe S, Lennard MS, Tucker GT, et al. The effect of paroxetine and other specific serotonin re-uptake inhibitors on cytochrome P450IID6 activity in human liver microsomes. Br J Clin Pharmacol 1991; 32: 658P-9P
41. Bloomer JC, Woods FR, Haddock RE, et al. The role of cyto-chrome P4502D6 in the metabolism of paroxetine by human liver microsomes. Br J Clin Pharmacol 1992; 33: 521-3
42. Sindrup SH. Brøsen K, Gram LF, et al. The relationship be-tween paroxetine and the sparteine oxidation polymorphism. Clin Pharmacol Ther 1992; 51: 278-87
43. Brøsen K, Hansen JG, Nielsen KK, et al. Inhibition by paroxetine of desipramine metabolism in extensive but not in poor metabolizers of sparteine. Eur J Clin Pharmacol 1993; 44: 349-55
44. Preskorn SH. Clinically relevant pharmacology of selective serotonin reuptake inhibitors: an overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clin Pharmacokinet 1997; 32 Suppl. 1: 1-21
45. Ozdemir V, Naranjo CA, Herrmann N, et al. paroxetine potentiates the central nervous system side effects of perphenazine: contribution of cytocrome P4502D6 inhibition in vivo. Clin Pharmacol Ther 1997; 62: 334-47
46. Tremaine LM, Welch WM, Ronfeld RA. Metabolism and disposition of the 5-hydroxytryptamine uptake blocker sertraline in the rat and dog. Drug Metab Dispos 1989; 17: 542-50
47. Sindrup SH, Brøsen K, Hansen MGJ, et al. Pharmacokinetics of citalopram in relation to the sparteine and the mephenytoin oxidation polymorphisms. Ther Drug Monit 1993; 15: 11-7
48. Baumann P, Nil R, Souche A, et al. 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 1996; 16: 307-14
49. Kobayashi K, Chiba K, Yagi T, et al. Identification of cytochrome P450 isoforms involved in citalopram N-demethylation by human liver microsomes. J Pharmacol Exp Ther 1997; 280: 927-33
50. Rochat B, Amey M, Baumann P. Analysis of enantiomers of citalopram and its demethylated metabolites in plasma of depressive patients using chiral reverse-phase liquid chromatography. Ther Drug Monit 1995; 17: 273-9
51. Foglia JP, Pollock BG, Kirshner MA, et al. Plasma levels of citalopram enantiomers and metabolites in elderly patients. Psychopharmacol Bull 1997; 33: 109-12
52. Rochat B, Amey M, Gillet M, et al. Identification of three cytochrome P450 isozymes involved in N-demethylation of citalopram enantiomers in human liver microsomes. Pharmacogenetics 1997; 7: 1-10
53. Bondolfi G, Chautems C, Rochat B, et al. Non-response to citalopram in depressive patients: pharmacokinetic and clinical consequences of a fluvoxamine augmentation. Psychopharmacology 1996; 128: 421-5
54. Torok-Both GA, Baker GB, Coults RT, et al. Simultaneous determination of fluoxetine and norfluoxetine enantiomers in biological samples by gas chromatography with electron-capture detection. J Chromatogr B 1992; 579: 99-106
55. Fjordside L, Jeppesen U, Eap CB et al. The stereoselective metabolism of fluoxetine in poor and extensive metabolisers of sparteine [abstract]. Eur J Clin Pharmacol 1997; Suppl. I: A127
56. Fuller RW, Snoddy HD, Perry KW. Importance of duration of drug action in the antagonism of p-chloroamphetamine depletion of brain serotonin-comparison of fluoxetine and chlorimipramine. Biochem Pharmacol 1978; 27: 193-8
57. Anelli M, Bizzi A, Caccia S, et al. Anorectic activity of fluoxetine and norfluoxetine in mice, rats and guinea-pigs. J Pharm Pharmacol 1992; 44: 696-8
58. Caccia S, Fracasso C, Garattini S, et al. Effects of short- and long-term administration of fluoxetine on the monoamine content of rat brain. Neuropharmacology 1992; 31: 343-7
59. Caccia S, Anelli M, Codegoni AM, et al. The effect of single and repeated anorectic doses of 5-hydroxytryplamine uptake inhibitors on indole levels in rat brain. Br J Pharmacol 1993; 110: 355-9
60. Altamura AC, Moro AR, Percudani M. Clinical pharmacokinetics of fluoxetine. Clin Pharmacokinet 1994; 26: 201-14
61. Hamelin BA, Turgeon J, Vallée F et al. The disposition of fluoxetine but not sertraline is altered in poor metabolizers of debrisoquin. Clin Pharmacol Ther 1996; 60: 512-21
62. Otton SV, WU D, Joffe RT, et al. Inhibition by fluoxetine of cytochrome P4562D6 activity. Clin Pharmacol Ther 1993; 53: 401-9
63. Harvey A, Preskora S. Cytochrome P450 enzymes: interpretation of their interactions with selective serotonin reuptake inhibitors. Part II. J Clin Psychopharmacol 1996; 16: 345-55
64. Brosen K. Are pharmacokinetic drug interactions with the SSRIS and issue? Int Clin psychopharmacol 1996; 11 Suppl. 1: 23-7
65. Meyer UA, Amrein R, Balant LP et al. Antidepressants and drug-metabolizing enzymes: expert group report. Acta Psychiatr Scand 1996; 93: 71-9
66. Bertilsson L, Dahl M-L, Tybring G. Pharmacogenetics of antidepressants: clinical aspects. Acta Psychiatr Scand Suppl 1997; 391: 14-21
67. Sproule BA, Naranjo CA, Bremner KE, et al. Selective serolonin reuptake inhibitors and CNS drug interactions. Clin Pharmacokinet 1997; 33: 454-71
68. Zussman BD, Davie CC, Fowles SE, et al. Sertraline, like other SSRIs, is a significant inhibitor of desipramine metabolism in vivo. Br J Clin Pharmacol 1995; 39: 550P
69. Alderman J, Preskorn SH, Greenblatt DJ, et al. desipramine pharmacokinetics when coadministered with paroxetine or sertraline in extensive metabolizers. J Clin Psychopharmacol 1997; 17: 284-91
70. Kurtz DL, Bergstrom RF, Goldberg MJ, Cerimele BJ. The effect of sertraline on the pharmacokinetics of desipramine and imipramine. Clin Pharmacol Ther 1997; 62: 145-56
71. Carson SW. Pharmacokinetic and pharmacodynamic drug interactions with polypharmacotherapy of treatment-resistant affective and obsessive-compulsive disorders Psychopharmacol Bull 1996; 32: 555-68
72. Preskorn SH, Alderman J, Greenblatt DJ, et al. Sertraline does not inhibit cytochrome P4503A-mediated drug metabolism in vivo. Psychopharmacol Bull 1997; 33: 659
73. Sprouse J, Clarke T, Reynolds L, et al. Comparison of the effects of sertraline and its metabolite desmethylsertraline on blockade of central 5-HT reuptake in vivo. Neuropsychopharmacology 1996; 14: 225-31
74. Fuller RW, Hemrick-Luecke SK, Littlefield ES, et al. Comparison of desmethylsertraline with sertraline as a monoamine uptake inhibitor in vivo. Prog Neuropsychopharmacol 1995; 19: 135-49
75. Garattini S, Bizzi A, Caccia S, et al. Progress report on the anorectic effects of dexfenfluramine, fluoxetine and sertraline. Int J Obes Relat Metab Disord 1992; 16 Suppl. 3: S43-50
76. Puozzo C, Leonard BE. Pharmacokinetics of milnacipran in comparison with other antidepressants. Int Clin Psychopharmacol 1996; 11 Suppl. 4: 15-27
77. Briley M, Prost JF, Moret C. Preclinical pharmacology of milnacipran. Int Clin Psychopharmacol 1996; 11 Suppl. 4: 10-4
78. Muth RA, Haskins JT, Mover JA, et al. Antidepressant biochemical profile of the novel bicyclic compound Wy-45,030, an ethyl cyclohexanol derivative. Biochem Pharmacol 1986; 35: 4493-7
79. Artigas F. Selective serotonin/noradrenaline reuptake inhibitors (SNRIs): pharmacology and therapeutic potential in the treatment of depressive disorders. CNS Drugs 1995; 4: 79-89
80. Bonnaud B, Cousse H, Mouzin G, et al. 1-Aryl-2-(aminoethyl) cyclopropanecarboxylic acid derivatives: a new series of potential antidepressants. J Med Chem 1987; 30: 318-25
81. Morton WA, Sonne SC, Verga MA. Venlataxine: a structurally unique and novel antidepressant. Ann Pharmacother 1995; 29: 387-95
82. Troy SM, Schultz RW, Parker VD, et al. The effect of renal disease on the disposition of venlafaxine. Clin Pharmacol Ther 1994; 56: 14-21
83. Wang CP, Howell SR, Scatina J, et al. The disposition of venlafaxine enantiomers in dogs, rats, and humans receiving venlafaxine. Chirality 1992; 4: 84-90
84. 14C-venlafaxine in mouse, rat, dog, rhesus monkey and man. Xenobiotica 1993; 23: 349-59
85. Muth KA, Mover JA, Haskins JT, et al. Biochemical, neurophysiological, and behavioral effects of Wy-45,233 and other identified metabolites of the antidepressant venlafaxine. Drug Dev Res 1991; 23: 191-9
86. Otton SV, Ball SE, Cheung SW, et al. Venlafaxine oxidation in vitro is catalysed by CYP2D6. Br J Clin Pharmacol 1996; 41: 149-56
87. von Moltke LL, Greenblatt DJ, Duan SX, et al. Phenacetin O-deethylation by human liver microsomes in vitro: inhibition by chemical probes, SSRI antidepressants, nefazodone and venlafaxine. Psychopharmacology 1996; 128: 398-407
88. Otton SV, Ball SE, Cheung SW, et al. Comparative inhibition of the polymorphic enzyme CYP2D6 by venlafaxine (VF) and other 5HT uptake inhibitors. Clin Pharmacol Ther 1994; 55: 141
89. Ball SE, Ahern D, Scatina J, et al. Venlafaxine: in vitro inhibition of CYP2D6 dependent imipramine and desipramine metabolism. Comparative studies with selected SSR1s, and effects on human hepatic CYP3A4, CYP2C9 and CYPIA2. Br J Clin Pharmacol 1997; 43: 619-26
90. Troy SM, Lucki I, Peirgies AA, et al. Pharmacokinetic and pharmacodynamic evaluation of the potential drug interaction between venlafaxine and diazepam. J Clin Pharmacol 1995; 35: 410-9
91. Ketter TA, Flockhart DA, Post RM, et al. The emerging role of cytochrome P450 3A in psychopharmacology. J Clin Psychopharmacol 1995; 15: 387-98
92. Ereshefsky L. Drug-drug interactions involving antidepressants: focus on venlafaxine. J Clin Psychopharmacol 1996; 16 Suppl. 2: 37S-50S
93. Melloni P, Della Torre A, Lazzari E, et al. Configuration studies on 2[α-ethoxyphenoxy][benzyl]morpholine FCE 20124. Tetrahedron 1985; 41: 1393-9
94. Melloni P, Carniel G, Della Torre A, et al. Potential antidepressant agents, α-aryloxy-benzyl derivatives of ethanolamine and morpholine. Eur J Med Chem Chim Ther 1984; 19: 235-42
95. Strolin Benedetti M, Frigerio E, Tocchetti P, et al. Stereoscleclive and species-dependent kineties of reboxetine in mouse and rat. Chirality 1995; 7: 285-9
96. Renshaw PF, Guimaraes AR, Fava M, et al. Accumulation of fluoxetine and norfluoxetine in human brain during therapeutic administration. Am J Psychiatry 1992; 149: 1592-4
97. Bergami A, Fracasso C, Garattini S, et al. Brain uptake and acute indole-depleting effect of dexfenfluramine in squirrel monkeys after a high-dose regimen. Pharm Sci 1995; 1: 45-8
98. Dostert P, Benedetti MS, Poggesi I. Review of the pharmacokinetics and metabolism of reboxetine, a selective noradrenaline reuptake inhibitor. Eur Neuropsychopharmacol 1997; 7 Suppl. 1: S23-35
99. Cocchiara G, Battaglia R, Pevarello P, et al. Comparison of the disposition and of the metabolic patterns of reboxetine, a new antidepressant, in the rat, dog, monkey and man. Eur J Drug Metab Pharmacokinet 1991; 16: 231-9
100. Pellizzoni C, Poggesi I, Jørgensen NP, et al. Pharmacokinetics of reboxetine in healthy volunteers: single against repeated oral doses and lack of enzymatic alterations. Biopharm Drug Dispos 1996; 17: 623-33
101. Edwards DMF, Pellizzoni C, Breuel HP, et al. Pharmacokinetics of reboxetine in healthy volunteers: single oral doses, linearity and plasma protein binding. Biopharm Drug Dispos 1995; 16: 443-60
102. Davis R, Whittington R, Bryson HM. Nefazodone: a review of its pharmacology and clinical efficacy in the management of major depression. Drugs 1997; 53: 608-36
103. Mayol RF, Cole CA, Luke GM, et al. Characterization of the metabolites of the antidepressant drug nefazodone in human urine and plasma. Drug Metab Dispos 1994; 22: 304-11
104. Caccia S, Fong MH, Garattini S, et al. Plasma concentrations of trazodone and 1-(3-chlorophenyl)-piperazine in man after a single oral dose of trazodone. J Pharm Pharmacol 1982; 34: 605-6
105. Caccia S, Garattini S. 1-Arylpiperazine as active metabolites of (4-substituted aryl-1-piperazinyl)alkyl heterocyclic drugs. Acta Pharm Jugosl 1990; 40: 441-60
106. Caccia S, Vigano GL, Mingardi G, et al. Clinical pharmacokinetics of oral buspirone in patients with impaired renal function. Clin Pharmacokinet 1988; 14: 171-7
107. 2-adrenoceptor antagonist activity of ipsapirone and gepirone is mediated by their common metabolite 1-(2-pyrimidinyl)-piperazine (PmP). Eur J Pharmacol 1988; 151: 365
108. Schmider J, Greenblalt DJ, von Moltkr LL, et al. Inhibition of cytochrome P450 by nefazodone in vitro: studies of dextromethorphan O- and N-demethylation. Br J Clin Pharmacol 1996; 41: 339-43
109. Greene DS, Barbhaiya RH. Clinical pharmacokinetics of nefazodone. Clin Pharmacokinet 1997; 33: 260-75
110. Barbhaiya RH, Buch AB, Greene DS. Single and multiple dose pharmacokinetics of nefazodone in subjects classified as extensive and poor metabolizers of dextromethorphan. Br J Clin Pharmacol 1996; 42: 573-81
111. Marino MR, Langenbacher KM, Uderman HD. Interaction of nefazodone (N) and fluoxetine (F). Clin Pharmacol Ther 1996; 59: 180
112. Yasui N, Otani K, Kaneko S, et al. Inhibition of trazodone metabolism of thioridazine in humans. Ther Drug Monit 1995; 17: 333-5
113. Hamik A, Peroutka SJ. 1-(m-chlorophenyl)piperazine (mCPP) interactions with neurotransmitter receptors in the human brain. Biol Psychiatry 1989; 25: 569-75
114. Murphy DL, Lesch KP, Aulakh CS, et al. Serotonin-selective arylpiperazines with neuroendocrine, behavioral, temperature, and cardiovascular effects in humans. Pharmacol Rev 1991; 43: 527-50
115. Benjamin J, Greenberg BD, Murphy DL. Daily administration of m-chlorophenylpiperazine to healthy human volunteers rapidly attenuates many of its behavioral, hormonal, cardio-vascular and temperature effects. Psychopharmacology 1996; 127: 140-9
116. Barbhaiya RH, Buch AB, Greene DS. A study of the effect of age and gender on the pharmacokinetics of nefazodone after single and multiple doses. J Clin Psychopharmacol 1996; 16: 19-25
117. Barbhaiya RH, Shukla UA, Greene DS. Single-dose pharmacokinetics of nefazodone in healthy young and elderly subjects and in subjects with renal or hepatic impairment. Eur J Clin Pharmacol 1995; 49: 221-8
118. Barbhaiya RH, Brady ME, Shukla UA, et al. Steady-state pharmacokinetics of nefazodone in subjects with normal and impaired renal function. Eur J Clin Pharmacol 1995; 49: 229-35
119. Barbhaiya RH, Shukla UA, Natarajan CS, et al. Single- and multiple-dose pharmacokinetics of nefazodone in patients with hepatic cirrhosis. Clin Pharmacol Ther 1995; 58: 390-8
120. Mocaër E, Rettori MC, Kamoun A. Pharmacological antidepressive effects and tianeptine-induced 5-HT uptake increase. Clin Neuropharmacol 1988; 11 Suppl. 2: S32-42
121. Mennini T, Garattini S. Neurobiology of tianeptine: a new pharmaceutic agent. Presse Med 1991; 20: 1823-7
122. Ansseau M. The paradox of tianeptine. Eur Psychiatry 1993; 8 Suppl. 2: 89S-93S
123. Wilde Mi, Benfield P. Tianeptine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depression and coexisting anxiety and depression. Drugs 1995; 49: 411-39
124. Grislain L, Gele P, Bertrand M, et al. The metabolic pathways of tianeptine, a new antidepressant, in healthy volunteers. Drug Metab Dispos 1990; 18: 804-8
125. Oluyomi AO, Datla KP, Curzon G. Effects of the (+) and (-)-enantiomers of the antidepressant drug tianeptine on 5-HTP-induced behaviour. Neuropharmacology 1997; 36: 383-7
126. Larrey D, Tinel M, Letteron P, et al. Metabolic activation of the new tricyclic antidepressant tianeptine by human liver cytochrome P450. Biochem Pharmacol 1990; 40: 545-50
127. Couet W, Girault J, Lutrille F, et al. Kinetic profiles of tianeptine and its MCS metabolite in plasma, blood and brain after single and chronic intraperitoneal administration in the rat. Eur J Drug Metab Pharmacokinet 1990; 15: 69-74
128. Carlhant D, Le Garrec J, Guedes Y, et al. Pharmacokinetics and bioavailability of tianeptine in the elderly. Drug Invest 1990; 2: 167-72
129. Demotes-Mainard F, Galley P, Manciet G, et al. Pharmacokinetics of the antidepressant tianeptine at steady state in the elderly. J Clin Pharmacol 1991; 31: 174-8
130. Salvadori C, Merdjan H, Brouard R, et al. Tianeptine and its main metabolite. Disposition in chronic renal failure and haemodialysis. Fundam Clin Pharmacol 1990; 4: 663-71
131. Royer RJ, Royer-Morrot MJ, Paille F, et al. Tianeptine and its main metabolite. Pharmacokinetics in chronic alcoholism and cirrhosis. Clin Pharmacokinet 1989; 16: 186-91
132. Sitsen JMA, Zivkov M. Mirtazapine: clinical profile. CNS Drugs 1995; 4 Suppl. 1: 39-48
133. Nutt D. Mirtazepine: pharmacology in relation to adverse effects. Acta Psychiatr Scand 1997; 96 Suppl. 391: 31-7
134. de Boer Th, Maura G, Raiteri M, et al. Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, ORG 3770 and its enantiomers. Neuropharmacology 1988; 27: 399-408
135. Davis R, Wilde MI. Mirtazapine: a review of its pharmacology and therapeutic potential in the management of major depression. CNS Drugs 1996; 389-402
136. Sandker GW, Vos RME, Delbressine LPC, et al. Metabolism of three pharmacologically active drugs in isolated human and rat hepatocytes: analysis of interspecies variability and comparison with metabolism in vivo. Xenobiotica 1994; 24: 143-55
137. Dahl M-L, Voortman G, Alm C, et al. In vitro and in vivo studies on the disposition of mirtazepine in humans. Clin Drug Invest 1997; 13: 37-46
138. Poirier MF, Olié JP, Loo H, et al. Activité antidépressive, caractéristiques pharmacocinétiques et propretés biochimiques de la cimoxatone, un nouvel IMAO-A réversible. Encéphale 1983; IX: 331-43
139. Fitton A, Faulds D, Goa KL. Moclobemide: a review of its pharmacological properties and therapeutic use in depressive illness. Drugs 1992; 43: 561-96
140. Fulton B, Benfield P. Moclobemide: an update of its pharmacological properties and therapeutic use. Drugs 1996; 52: 450-74
141. Volz HP, Gleiter CH, Struck M, et al. Brofaromine: insight into the nature of drug development. CNS Drugs 1995; 3: 1-8
142. Mayersohn M, Guentert TW. Clinical pharmacokinetics of the monoamine oxidase-A inhibitor moclobemide. Clin Pharmacokinet 1995; 29: 292-32
143. Schoerlin MP, Mayersohn M, Korn A, et al. Disposition kinetics of moclobemide, a monoamine oxidase-A enzyme inhibitor: single and multiple dosing in normal subjects. Clin Pharmacol Ther 1987; 42: 395-404
144. Schoerlin MP, Horber FF, Frey FJ, et al. Disposition kinetics of moclobemide, a new MAO-A inhibitor, in subjects with impaired renal function. J Clin Pharmacol 1990; 30: 272-84
145. Stoeckel K, Pfefen JP, Mayersohn M, et al. Absorption and disposition of moclobemide in patients with advanced age or reduced liver or kidney function. Acta Psychiatr Scand 1990; Suppl. 360: 94-97
146. Jauch R, Griesser E, Oesterhelt G, et al. Biotransformation of moclobemide in humans. Acta Psychiatr Scand 1990; Suppl. 360: 87-90
147. Schoerlin MP, Da Prada M. Species-specific biotransformation of moclobemide: a comparative study in rats and humans. Acta Psychiatr Scand 1990; Suppl. 360: 108-10
148. Da Prada M, Kettler R, Keller HH, et al. Neurochemical profile of moclobemide, a short-acting and reversible inhibitor of monoamine oxidase type A. J Pharmacol Exp Ther 1989; 248: 400-8
149. Fritze J, Laux G, Sofic K, et al. Plasma moclobemide and metabolites: lack of correlation with clinical response and biogenic amines. Psychopharmacology 1989; 99: 252-6
150. Guentert TW, Gram LF, Grange S, et al. Reversible interaction of moclobemide with CYP2D6 and CYP2C9. Clin Pharmacol Ther 1994; 55: P1-57
151. Gram LF, Brøsen K, and the Danish University Antidepressant Group. Moclobemide treatment causes a substantial rise in the sparteine metabolic ratio. Br J Clin Pharmacol 1993; 35: 649-52
152. Spigset O, Granberg K, Hägg S, et al. Non-linear fluvoxamine disposition. Br J Clin Pharmacol 1998; 45: 257-63
153. Sperker B, Backman JT, Kroemer HK. The role of β-glucuronidase in drug disposition and drug targeting in humans. Clin Pharmacokinet 1997; 33: 18-31
154. Campbell B, Dard-Brunelle B, Caccia S. The use of pharmacokinetics in the assessment of dexfenfluramine safety. In: Nicolaidis S, editor. Obesity management and Redux™. San Diego: Academic Press, 1997: 65-80
155. Matzke GR, St Peter WL. Clinical pharmacokinetics 1990. Clin Pharmacokinet 1990; 18: 1-19
156. Bartels, Albert K. Detection of Psychoative drugs using 19F MR spectroscopy. J Neural Transm Gen Sect 1995; 99: 1-6
157. Kennedy SH, Javanmard M, Vaccarino FJ. A review of functional neuroimaging in mood disorders: positron emission tomography and depression. Can J Psychiatry 1997; 42: 467-75