Pharmacokinetics and pharmacodinamics of psychotropic drugs: Effect of sex

CNS Spectrums

Volumn 18, Issue 3, 2013, Pages 118-127

  Marazziti, Donatella ^a   Baroni, Stefano ^a   Picchetti, Michela ^a   Piccinni, Armando ^a   Carlini, Marina ^a   Vatteroni, Elena ^a   Falaschi, Valentina ^a   Lombardi, Amedeo ^a   Dell'osso, Liliana ^a  

^a UNIVERSITY OF PISA   (Italy)

Author keywords

Antipsychotics; benzodiazepines; gender; psychotropic drugs; SSRIs; tricyclics

Indexed keywords

CYTOCHROME; PSYCHOTROPIC AGENT;

ANIMAL; BIOTRANSFORMATION; FEMALE; HUMAN; INTESTINE ABSORPTION; MALE; METABOLISM; REVIEW; SEXUAL DEVELOPMENT; TISSUE DISTRIBUTION;

ANIMALS; BIOTRANSFORMATION; CYTOCHROMES; FEMALE; HUMANS; INTESTINAL ABSORPTION; MALE; PSYCHOTROPIC DRUGS; SEX CHARACTERISTICS; TISSUE DISTRIBUTION;

MLCS; MLOWN;

EID: 84881232061     PISSN: 10928529     EISSN: 21656509     Source Type: Journal    
DOI: 10.1017/S1092852912001010     Document Type: Review

References (109)

1. Fankhauser, MP. Psychiatric disorders in women: psychopharmacologic treatments. J Am Pharm Assoc (Wash DC). 1997; 6: 667–678.
2. Frezza, M, di Padova, C, Pozzato, G, et al. High blood alcohol levels in women: the role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. N Engl J Med. 1990; 322: 95–99.
3. Hamilton, J, Yonkers, K. Sex differences in pharmacokinetics of psychotropic medication, part I: physiological basis for effects. In: Jensvold M, Halbreich U, Hamilton J, eds. Psychopharmacology and Women: Sex, Gender, and Hormones. Washington, DC: American Psychiatric Press; 1996: 11–42.
4. Rao, S, Read, N, Brown, C, et al. Studies on the mechanism of bowel disturbance in ulcerative colitis. Gastroenterology. 1987; 93: 934–940.
5. Grossman, M, Kirsner, J, Gillespie, I. Basal and histalog-stimulated gastric secretion in control subjects and in patients with peptic ulcer or gastric cancer. Gastroenterology. 1963; 45: 14–26.
6. Pollock, BG. Gender differences in psychotropic drug metabolism. Psychopharmacol Bull. 1997; 33: 235–241.
7. Nicolas, JM, Espie, P, Molimard, M. Gender and interindividual variability in pharmacokinetics. Drug Metab Rev. 2009; 41(3): 408–421.
8. Chen, ML, Lee, SC, Ng, MJ, et al. Pharmacokinetic analysis of bioequivalence trials: implications for sex-related issues in clinical pharmacology and biopharmaceutics. Clin Pharmacol Ther. 2000; 68(5): 510–521.
9. Mayersohn, M. Drug disposition. In: Conrad K, Bressler R, eds. Drug Therapy for the Elderly. St. Louis, MO: CV Mosby; 1982: 31–63.
10. Yonkers, KA, Kando, JC, Cole, JO, et al. Gender differences in pharmacokinetics and pharmacodynamics of psychotropic medication. Am J Psychiatry. 1992; 149: 587–595.
11. Greenblatt, D, Sellers, E, Shader, R. Drug disposition in old age. N Engl J Med. 1982; 306: 1081–1088.
12. Sweet, R, Pollock, B, Wright, B, et al. Single and multiple dose bupropion pharmacokinetics in elderly patients with depression. J Clin Pharmacol. 1995; 35: 876–884.
13. Brown, SL, Salive, ME, Guralnik, JM, et al. Antidepressant use in the elderly: association with demographic characteristics, health-related factors, and health care utilization. J Clin Epidemiol. 1995; 48: 445–453.
14. Simoni Wastila, L. Gender and psychotropic drug use. Med Care. 1998; 36: 88–94.
15. Gleiter, CH, Gundert-Remy, U. Gender differences in pharmacokinetics. Eur J Drug Metab Pharmacokinet. 1996; 21: 123–128.
16. Hashimoto, S, Miwa, M, Akasofu, K, Nishida, E. Changes in 40 serum proteins of post-menopausal women. Maturitas. 1991; 13: 23–33.
17. Blain, PG, Mucklow, JC, Rawlins, MD, et al. Determinants of plasma alpha 1-acid glycoprotein (AAG) concentrations in health. Br J Clin Pharmacol. 1985; 20: 500–502.
18. Kishino, S, Nomura, A, Itoh, S, et al. Age- and gender-related differences in carbohydrate concentrations of alpha1-acid glycoprotein variants and the effects of glycoforms on their drug-binding capacities. Eur J Clin Pharmacol. 2002; 58: 621–628.
19. Tuck, CH, Holleran, S, Berglund, L. Hormonal regulation of lipoprotein(a) levels: effects of estrogen replacement therapy on lipoprotein(a) and acute phase reactant in postmenopausal women. Arterioscler Thromb Vasc Biol. 1997; 17: 1822–1829.
20. Israili, ZH, Dayton, PG. Human alpha-1-glycoprotein and its interactions with drugs. Drug Metab Rev. 2001; 33: 161–235.
21. 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; 1: 1–21.
22. Palmer, K, Benfield, P. Fluvoxamine: an overview of its pharmacological properties and review of its therapeutic potential in nondepressive disorders. CNS Drugs. 1994; 1: 57–87.
23. Yonkers, K, Hamilton, J. Sex differences in pharmacokinetics of psychotropic medication, part II: effects on selected psychotropics. In: Jensvold M, Halbreich U, Hamilton J, eds. Psychopharmacology and Women: Sex, Gender, and Hormones. Washington, DC: American Psychiatric Press; 1996: 43–72.
24. Fredericson, O. Preliminary studies of the kinetics of citalopram in man. Eur J Clin Pharmacol. 1978; 14: 69–73.
25. Kristensen, C. Imipramine serum protein binding in healthy subjects. Clin Pharmacol Ther. 1983; 34: 689–694.
26. Wilson, K. Sex-related differences in drug disposition in man. Clin Pharmacokinet. 1984; 9: 189–202.
27. Preskorn, S. Clinical Pharmacology of Selective Serotonin Reuptake Inhibitors. Professional Communications, Inc., Caddo; 1996.
28. Kalra, B. Cytochrome P450 enzyme isoforms and their therapeutic implications: an update. Indian J Med Sci. 2007; 61(2): 102–116.
29. Zhou, S, Chan, SY, Goh, BC, et al. Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs. Clin Pharmacokinet. 2005; 44(3): 279–304.
30. Pollock, B, Altieri, L, Kirshner, M, et al. Debrisoquine hydroxylation phenotyping in geriatric psychopharmacology. Psychopharmacol Bull. 1992; 28: 257–263.
31. Wadelius, M, Darj, E, Frenne, G, Rane, A. Induction of CYP2D6 in pregnancy. Clin Pharmacol Ther. 1997; 62: 400–407.
32. Kashuba, AD, Nafziger, AN, Kearns, GL, et al. Quantification of intraindividual variability and the influence of menstrual cycle phase on CYP2D6 activity as measured by dextromethorphan phenotyping. Pharmacogenetics. 1998; 8: 403–410.
33. Labbe, L, Sirois, C, Pilote, S, et al. Effects of gender, sex hormones, time variables and physiological urinary pH on apparent CYP2D6 activity as assessed by metabolic ratios of marker substrates. Pharmacogenetics. 2000; 10: 425–438.
34. McCune, JS, Lindley, C, Decker, JL, et al. Lack of gender differences and large intrasubject variability in cytochrome P450 activity measured by phenotyping with dextromethorphan. J Clin Pharmacol. 2001; 41: 723–731.
35. Brosen, K. Isoenzyme specific drug oxidation: genetic polymorphism and drug-drug interactions. Nord J Psychiatry. 1993; 47(30): 21–26.
36. Ketter, T, Flockhart, D, Post, R, et al. The emerging role of cytochrome P4503A in psychopharmacology. J Clin Psychopharmacol. 1995; 15: 387–395.
37. Edeki, T, Goldstein, JA, de Morais, SMF, et al. Genetic polymorphism of S-mephenytoin 4′-hydroxylation in African-Americans. Pharmacogenetics. 1996; 6: 357–363.
38. Sviri, S, Shpizen, S, Leitersdorf, E, Levy, M, Caraco, Y. Phenotypic-genotypic analysis of CYP2C19 in the Jewish Israeli population. Clin Pharmacol Ther. 1999; 65: 275–281.
39. Price Evans, DA, Krahn, P, Narayanan, N. The mephenytoin (cytochrome P450 2C 19) and dextromethorphan (cytochrome P450 2D6) polymorphisms in Saudi Arabians and Filipinos. Pharmacogenetics. 1995; 5: 64–72.
40. Tamminga, WJ, Wemer, J, Oosterhuis, B, et al. CYP2D6 and CYP2C19 activity in a large population of Dutch healthy volunteers: indications for oral contraceptive-related gender differences. Eur J Clin Pharmacol. 1999; 55: 177–185.
41. Hagg, S, Spigset, O, Dahlqvist, R. Influence of gender and oral contraceptives on CYP2D6 and CYP2C19 activity in healthy volunteers. Br J Clin Pharmacol. 2001; 51: 169–177.
42. Anderson, GD. Sex differences in drug metabolism: cytochrome P-450 and uridine diphosphate glucuronosyltransferase. J Gend Specif Med. 2002; 5: 25–33.
43. Scripture, C, Pieper, J. Clinical pharmacokinetics of fluvastatin. Clin Pharmacokinet. 2001; 40: 263–281.
44. Ford, J, Truman, C, Wilcock, G, et al. Serum concentrations of tacrine hydrochloride predict its adverse effects in Alzheimer's disease. Clin Pharmacol Ther. 1993; 53: 691–695.
45. Hartter, S, Wetzel, H, Hammes, E, et al. Inhibition of antidepressant demethylation and hydroxylation by fluvoxamine in depressed patients. Psychopharmacology. 1993; 110: 302–308.
46. Wrighton, SA, Stevens, JC. The human hepatic cytochrome P450 involved in drug metabolism. Crit Rev Toxicol. 1992; 22: 1–12.
47. Jennings, TS, Nafziger, AN, Davidson, L, et al. Gender differences in hepatic induction and inhibition of theophylline pharmacokinetics and metabolism. J Lab Clin Med. 1993; 122: 208–217.
48. Bock, K, Schrenk, D, Forster, A, et al. The influence of environmental and genetic factors on CYP2D6, CYP1A2 and UDP-glucuronosyltransferases in man using sparteine, caffeine and paracetamol as probes. Pharmacogenetics. 1994; 4: 209–219.
49. Relling, MV, Lin, JS, Ayers, GD, Evans, WE. Racial and gender differences in N acetyltransferase, xanthine oxidase and CYP1A2 activities. Clin Pharmacol Ther. 1992; 52: 643–653.
50. Lane, HY, Chang, YC, Chang, WH, et al. Effects of gender and age on plasma levels of clozapine and its metabolites: analyzed by critical statistics. J Clin Psychiatry. 1999; 60: 36–43.
51. Callaghan, JT, Bergstrom, RF, Ptak, LR, Beasley, CM. Olanzapine: pharmacokinetic and pharmacodynamic profile. Clin Pharmacokinet. 1999; 37: 177–186.
52. Nemeroff, C, De Vane, C, Pollock, B. Newer antidepressants and the cytochrome P450 system. Am J Psychiatry. 1996; 153: 311–320.
53. Schwartz, JB. The influence of sex on pharmacokinetics. Clin Pharmacokinet. 2003; 42: 107–121.
54. Karim, A, Slater, M, Bradford, D, et al. Oral antidiabetic drugs: bioavailability assessment of fixed-dose combination tablets of pioglitazone and metformin. Effect of body weight, gender, and race on systemic exposures of each drug. J Clin Pharmacol. 2007; 47(1): 37–47.
55. Lin, Y, Anderson, GD, Kantor, E, Ojemann, LM, Wilensky, AJ. Differences in the urinary excretion of 6-beta-hydroxycortisol/cortisol between Asian and Caucasian women. J Clin Pharmacol. 1999; 39: 578–582.
56. Gaudry, SE, Sitar, DS, Smyth, DD, McKenzie, JK, Aoki, FY. Gender and age as factors in the inhibition of renal clearance of amantadine by quinine and quinidine. Clin Pharmacol Ther. 1993; 54(1): 23–27.
57. Berg, UB. Differences in decline in GFR with age between males and females: reference data on clearances of inulin and PAH in potential kidney donors. Nephrol Dial Transplant. 2006; 21(9): 2577–2582.
58. Hytten, FE, Chamberlain, G. Clinical Physiology in Obstetrics. Oxford, UK: Blackwell Scientific; 1980.
59. Silvaggio, T, Mattison, DR. Setting occupational health standards: toxicokinetic differences among and between men and women. J Occup Med. 1994; 36(8): 849–854.
60. Kim, JS, Nafziger, AN. Is it sex or is it gender? Clin Pharmacol Ther. 2000; 68(1): 1–3.
61. Fromm, MF. P-glycoprotein: a defense mechanism limiting oral bioavailability and CNS accumulation of drugs. Int J Clin Pharmacol Ther. 2000; 38(2): 69–74.
62. Yonkers, KA, Kando, JC, Cole, JO, et al. Gender differences in pharmacokinetics and pharmacodynamics of psychotropic medication. Am J Psychiatry. 1992; 149(5): 587–595.
63. Jerling, M, Merle, Y, Mentre, F, Mallet, A. Population pharmacokinetics of clozapine evaluated with the nonparametric maximum likelihood method. Br J Clin Pharmacol. 1997; 44: 447–453.
64. Lane, HY, Chang, YC, Chang, WH, et al. Effects of gender and age on plasma levels of clozapine and its metabolites: analyzed by critical statistics. J Clin Psychiatry. 1999; 60: 36–40.
65. Fabrazzo, M, Esposito, G, Fusco, R, Maj, M. Effect of treatment duration on plasma levels of clozapine and N-desmethylclozapine in men and women. Psychopharmacology. 1996; 124: 197–200.
66. Rostami-Hodjegan, A, Amin, AM, Spencer, EP, et al. Influence of dose, cigarette smoking, age, sex, and metabolic activity on plasma clozapine concentrations: a predictive model and nomograms to aid clozapine dose adjustment and to assess compliance in individual patients. J Clin Psychopharmacol. 2004; 24: 70–78.
67. Gex-Fabry, M, Balant-Gorgia, AE, Balant, LP. Therapeutic drug monitoring of olanzapine: the combined effect of age, gender, smoking, and comedication. Ther Drug Monit. 2003; 25: 46–53.
68. Kelly, DL, Conley, RR, Tamminga, CA. Differential olanzapine plasma concentrations by sex in a fixed-dose study. Schizophr Res. 1999; 40: 101–104.
69. Seeman, MV. Interaction of sex, age, and neuroleptic dose. Compr Psychiatry. 1983; 24: 125–128.
70. Morgenstern, H, Glazer, W. Identifying risk factors for tardive dyskinesia among long-term outpatients maintained with neuroleptic medication. Arch Gen Psychiatry. 1993; 50: 723–733.
71. Yassa, R, Jeste, D. Gender differences in tardive dyskinesia: a critical review of the literature. Schizophr Bull. 1992; 18: 701–715.
72. Browne, S, Roc, M, Lane, A, Gavin, N, Morris, M, Kinsella, A, Larkin, C, O'Calloghan, E. Quality of life in schizophrenia: relationship to sociodemographic factors, symptomology and tardive dyskinesi. Acte Psychiat Scan. 1996; 96: 79–87.
73. Wolbrette, D. Gender differences in the proarrhythmic potential of QT-prolonging drugs. Curr Womens Health Rep. 2002; 2: 105–109.
74. Hatta, K, Takahashi, T, Nakamura, H, et al. The association between intravenous haloperidol and prolonged QT interval. J Clin Psychopharmacol. 2001; 21: 257–261.
75. Kuruvilla, A, Peedicayil, J, Srikrishna, G, Kuruvilla, K, Kanagasabapathy, AS. A study of serum prolactin levels in schizophrenia: comparison of males and females. Clin Exp Pharmacol Physiol. 1992; 19: 603–606.
76. Naidoo, U, Kinon, BJ, Gilmore, JA, Liu, H, Halbreich, UM. Hyperprolactinemia in response to antipsychotic drugs: characterization across comparative clinical trials. Psychoneuroendocrinology. 2003; 28(2): 69–82.
77. Melkersson, K, Hulting, AL, Hall, K. Hormonal evaluation in schizophrenic patients treated with neuroleptics. Neuro Endocrinol Lett. 1999; 20: 199–204.
78. Allison, DB, Mentore, JL, Heo, M, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999; 156: 1686–1696.
79. Baptista, T, Kin, NM, Beaulieu, S, De Baptista, EA. Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives. Pharmacopsychiatry. 2002; 35: 205–219.
80. Hedenmalm, K, Hagg, S, Stahl, M, Mortimer, O, Spigset, O. Glucose intolerance with atypical antipsychotics. Drug Saf. 2002; 25: 1107–1116.
81. Sernyak, MJ, Leslie, DL, Alarcon, RD, Losonczy, MF, Rosenheck, R. Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia. Am J Psychiatry. 2002; 159: 561–566.
82. Grossman, ML, Kirsner, JB, Cillespie, LE. Basal and histalog-stimulated gastric secretion in control subjects and in patients with peptic ulcer or gastric cancer. Gastroenterology. 1963; 45: 14–26.
83. Hutson, WR, Roehrkasse, RL, Wald, A. Influence of gender and menopause on gastric emptying and motility. Gastroenterology. 1989; 96(1): 11–17.
84. Wald, A, Van Thiel, DH, Hoechstetter, L, et al. Gastrointestinal transit: the effect of the menstrual cycle. Gastroenterology. 1981; 80(6): 1497–1500.
85. Greenblatt, DJ, Friedman, H, Burstein, ES, et al. Trazodone kinetics: effect of age, gender, and obesity. Clin Pharmacol Ther. 1987; 42(2): 193–200.
86. Stewart, JJ, Berkel, HJ, Parish, RC, et al. Single-dose pharmacokinetics of bupropion in adolescents: effects of smoking status and gender. J Clin Pharmacol. 2001; 41(7): 770–778.
87. Greenblatt, DJ, Divoll, M, Harmatz, JS, Shader, RI. Oxazepam kinetics: effects of age and sex. J Pharmacol Exp Ther. 1980; 215(1): 86–91.
88. Greenblatt, DJ, Divoll, M, Abernethy, DR, Shader, RI. Physiologic changes in old age: relation to altered drug disposition. J Am Geriatr Soc. 1982; 30(11): S6–10.
89. Findling, RL, Nucci, G, Piergies, AA, et al. Multiple dose pharmacokinetics of paroxetine in children and adolescents with major depressive disorder or obsessive-compulsive disorder. Neuropsychopharmacology. 2006; 31(6): 1274–1285.
90. Bies, RR, Bigos, Kl, Pollock, BC. Gender differences in the pharmacokinetics and pharmacodynamics of antidepressants. J Gend Specif Med. 2003; 6: 12–20.
91. Hildebrandt, MG, Steyerberg, EW, Stage, KB, et al, for the Danish University Antidepressant Group. Are gender differences important for the clinical effects of antidepressants? Am J Psychiatry. 2003; 160: 1643–1650.
92. Mundo, E, Pirola, R, Bellodi, L, et al. Are gender differences in antiobsessional response related to different clomipramine metabolism? J Clin PsychopharmacoI. 2002; 22: 341–342.
93. Cohen, LC, Biederman, J, Wilens, TE, et al. Desipramine clearance in children and adolescents: absence of effect of development and gender. J Am Acad Child Adolesc Psychiatry. 1999; 38: 79–85.
94. Physicians’ Desk Reference. 57th ed. Montvale, NJ: Thomson P D R; 2003.
95. De Mendonca Lima, CA, Baumann, P, Braward-Amey, M, et al. Effect of age and gender on citalopram and desmethylcitalopram steady-state plasma concentrations in adults and elderly depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29: 952–956.
96. Reis, M, Chermß, MD, Carlsson, B, Bengtsson, F, for the Task Force for TDM of Escitalopram in Sweden. Therapeutic drug monitoring of escitalopram in an outpatient setting. Ther Drug Monit. 2007; 29: 758–766.
97. 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: 22–30.
98. Ferguson, JM, Hill, H. Pharmacokinetics of fluoxetine in elderly men and women. Gerontology. 2006; 52: 45–50.
99. Gex-Fabry, M, Eap, CB, Oneda, B, et al. CYP2D6 and ABCB1 genetic variability: influence on paroxetine plasma level and therapeutic response. Ther Drug Monit. 2008; 30: 474–482.
100. Physicians’ Desk Reference. 63rd ed. Montvale, NJ: Thomson Reuters; 2009.
101. Parker, G, Parker, K, Austin, MP, et al. Gender differences in response to differing antidepressant drug classes: two negative studies. Psychol Med. 2003; 33(8): 1473–1477.
102. Kornstein, SG, Schatzberg, AF, Thase, ME, et al. Gender differences in treatment response to sertraline versus imipramine in chronic depression. Am J Psychiatry. 2000; 157(9): 1445–1452.
103. Baca, E, Garcia-Garcia, M, Porras-Chavarino, A. Gender differences in treatment response to sertraline versus imipramine in patients with non-melancholic depressive disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2004; 28(1): 57–65.
104. Joyce, PR, Mulder, RT, Luty, SE, et al. Melancholia: definitions, risk factors, personality, neuroendocrine markers and differential antidepressant response. Aust N Z J Psychiatry. 2002; 36(3): 376–383.
105. Young, EA, Kornstein, SG, Marcus, SM, et al. Sex differences in response to citalopram: a STAR*D report. J Psychiatr Res. 2009; 43(5): 503–511.
106. Thase, ME, Entsuah, R, Cantillon, M, et al. Relative antidepressant efficacy of venlafaxine and SSRIs: sex-age interactions. J Womens Health (Larchmt). 2005; 14(7): 609–616.
107. Bano, S, Akhter, S, Afridi, MI. Gender based response to fluoxetine hydrochloride medication in endogenous depression. J Coll Physicians Surg Pak. 2004; 14(3): 161–165.
108. Marazziti, D, Baroni, S, Giannaccini, G, et al. Plasma fluvoxamine levels and OCD symptoms/response in adult patients. Hum Psychopharmacol. 2012; 27(4): 397–402.
109. Marazziti, D, Baroni, S, Faravelli, L, et al. Plasma clomipramine levels in adult patients with obsessive-compulsive disorder. Int Clin Psychopharmacol. 2012; 27(1): 55–60.