Clinical Pharmacokinetics

, Volume 24, Issue 6, pp 453–471 | Cite as

Clinical Pharmacokinetics of Alprazolam

Therapeutic Implications
  • David J. Greenblatt
  • C. Eugene Wright
Review Article Drug Disposition


Alprazolam is a triazolobenzodiazepine that is extensively prescribed in the Western world for the treatment of anxiety and panic disorders. Its benzodiazepine receptor binding characteristics are qualitatively similar to those of other benzodiazepines. The drug is metabolised primarily by hepatic microsomal oxidation, yielding α-hydroxy- and 4-hydroxy-alprazolam as principal initial metabolites. Both have lower intrinsic benzodiazepine receptor affinity than alprazolam and appear in human plasma at less than 10% of the concentrations of the parent drug. Plasma concentrations of the 4-hydroxy metabolite exceed those of the α-hydroxy derivative, but urinary recovery of α-hydroxy-alprazolam greatly exceeds that of 4-hydroxy-alprazolam. This may be explained by chemical instability of 4-hydroxy-alprazolam in vitro.

After single 1mg oral doses in humans, typical pharmacokinetic variables for alprazolam are: a peak plasma concentration 12 to 22 μg/L occurring 0.7 to 1.8h postdose, a volume of distribution of 0.8 to 1.3 L/kg, elimination half-life of 9 to 16h and clearance of 0.7 to 1.5 ml/min/kg. Absolute bioavailability of oral alprazolam averages 80 to 100%. Pharmacokinetics are dose-independent and are unchanged during multiple-dose treatment. On average, mean steady-state plasma alprazolam concentrations change by 10 to 12 μg/L for each daily dosage change of 1 mg/day.

Most studies show that alprazolam pharmacokinetics are not significantly influenced by gender. Clearance of alprazolam is reduced in many elderly individuals, even those who are apparently healthy. Clearance is significantly reduced in patients with cirrhosis. Renal disease causes reduced plasma protein binding of alprazolam (increased free fraction) and some data suggest reduced free clearance of alprazolam in such patients. Pharmacokinetics of alprazolam are not significantly altered in abstinent alcoholics or patients with panic disorder, and are not influenced by the phase of the menstrual cycle in women.

Coadministration of Cimetidine, fluoxetine, fluvoxamine or propoxyphene significantly impairs alprazolam clearance. However, alprazolam clearance is not altered by coadministration of propranolol, metronidazole, disulfiram, oral contraceptives or ethanol. Imipramine clearance may be impaired if alprazolam is coadministered. Alprazolam does not alter the pharmacokinetics of digoxin.

Although a therapeutic concentration range is not clearly established, some studies indicate that optimal reduction of anxiety associated with panic disorder occurs at steady-state plasma alprazolam concentrations of 20 to 40 μg/L. Concentrations higher than this may be needed for suppression of the actual panic attacks. Side effects associated with alprazolam (drowsiness, sedation, etc.) are consistent with its primary benzodiazepine agonist action and increase in frequency with higher steady-state plasma concentrations. As with other benzodiazepines, tolerance develops to the central depressant effects of alprazolam. Side effects diminish over time with continuous administration.

Because of its relatively short half-life, abrupt termination of alprazolam treatment can be followed by one or more discontinuation syndromes (recurrence, rebound or withdrawal). For this reason, alprazolam should be tapered rather than abruptly discontinued when treatment is stopped. Clinical consequences of alprazolam discontinuation are no different than those occurring after discontinuation of any benzodiazepine with a short half-life.


Clinical Pharmacology Panic Disorder Alprazolam Triazolam Digit Symbol Substitution Test 
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  1. Abernethy DR, Greenblatt DJ, Divoll M, Moschitto LJ, Harmatz JS, et al. Interaction of Cimetidine with the triazolobenzodiazepines alprazolam and triazolam. Psychopharmacology 80: 275–278, 1983PubMedCrossRefGoogle Scholar
  2. Abernethy DR, Greenblatt DJ, Divoll M, Smith RB, Shader RI. The influence of obesity on the pharmacokinetics of oral alprazolam and triazolam. Clinical Pharmacokinetics 9: 177–183, 1984PubMedCrossRefGoogle Scholar
  3. Abernethy DR, Greenblatt DJ, Morse DS, Shader RI. Interaction of propoxyphene with diazepam, alprazolam and lorazepam. British Journal of Clinical Pharmacology 19: 51–57, 1985PubMedCrossRefGoogle Scholar
  4. Adams WJ. Specific and sensitive high performance liquid chromatographic determination of alprazolam or triazolam. Analytical Letters 12: 657–671, 1979CrossRefGoogle Scholar
  5. Adams WJ, Bombardt PA, Brewer JE. Normal-phase liquid chromatographic determination of alprazolam in human serum. Analytical Chemistry 56: 1590–1594, 1984PubMedCrossRefGoogle Scholar
  6. Antal EJ, Grasela TH, Smith RB. An evaluation of population pharmacokinetics in therapeutic trials. Part III. Prospective data collection versus retrospective data assembly. Clinical Pharmacology and Therapeutics 46: 552–559, 1989PubMedCrossRefGoogle Scholar
  7. Arendt RM, Greenblatt DJ, Liebisch DC, Luu MD, Paul SM. Determinants of benzodiazepine brain uptake: lipophilicity versus binding affinity. Psychopharmacology 93: 7276, 1987CrossRefGoogle Scholar
  8. Atta-Politou J, Parissi-Poulou M, Dona A, Koutselinis A. A simple and rapid reserved phase high performance liquid chromatographic method for quantification of alprazolam and α-hydroxyalprazolam in plasma. Journal of Liquid Chromatography 14: 3531–3546, 1991CrossRefGoogle Scholar
  9. Bertilsson L, Aberg-Wistedt A, Liden A, Otani K, Spina E. Alprazolam does not inhibit the metabolism of nortriptyline in depressed patients or inhibit the metabolism of desipramine in human liver microsomes. Therapeutic Drug Monitoring 10: 231–233, 1988PubMedCrossRefGoogle Scholar
  10. Blyden GT, Scavone JM, Greenblatt DJ. Metronidazole impairs clearance of Phenytoin but not of alprazolam or lorazepam. Journal of Clinical Pharmacology 28: 240–245, 1988PubMedGoogle Scholar
  11. Carson SW, Wright CE, Millikin SP, Lyon J, Chambers JH. Pharmacokinetic evaluation of the combined administration of alprazolam (ALP) and clomipramine (CMI). Clinical Pharmacology and Therapeutics 51: 105, 1992Google Scholar
  12. Ciraulo DA, Antal EJ, Smith RB, Olson DR, Goldberg DA, et al. The relationship of alprazolam dose to steady-state plasma concentrations. Journal of Clinical Psychopharmacology 10: 27–32, 1990PubMedCrossRefGoogle Scholar
  13. Ciraulo DA, Barnhill JG, Boxenbaum HG, Greenblatt DJ, Smith RB. Pharmacokinetics and clinical effects of alprazolam following single and multiple oral doses in patients with panic disorder. Journal of Clinical Pharmacology 26: 292–298, 1986PubMedGoogle Scholar
  14. Ciraulo DA, Barnhill JG, Greenblatt DJ, Shader RI, Ciraulo AM, et al. Abuse liability and clinical pharmacokinetics of alprazolam in alcoholic men. Journal of Clinical Psychiatry 49: 333–337, 1988PubMedGoogle Scholar
  15. Dawson GW, Jue SG, Brogden RN. Alprazolam: a review of its pharmacodynamic properties and efficacy in the treatment of anxiety and depression. Drugs 27: 132–147, 1984PubMedCrossRefGoogle Scholar
  16. Dehlin O, Kullingsjo H, Liden A, Agrell B, Moser G, et al. Pharmacokinetics of alprazolam in geriatric patients with neurotic depression. Pharmacology and Toxicology 68: 121–124, 1991PubMedCrossRefGoogle Scholar
  17. Diquet B, Gujadhur L, Lamiable D, Warot D, Hayoun H, et al. Lack of interaction between disulfiram and alprazolam in alcoholic patients. European Journal of Clinical Pharmacology 38: 157–160, 1990PubMedCrossRefGoogle Scholar
  18. Eberts FS, Philopoulos Y, Reineke LM, Vliek RW. Disposition of 14C-alprazolam, a new anxiolytic-antidepressant, in man. Pharmacologist 22: 279, 1980Google Scholar
  19. Edinboro LE, Backer RC. Preliminary report on the application of a high performance liquid chromatographic method for alprazolam in postmortem blood specimens. Journal of Analytical Toxicology 9: 207–208, 1985PubMedGoogle Scholar
  20. Eller MG, Della-Coletta AA. Absence of effect of food on alprazolam absorption from sustained release tablets. Biopharmaceutics and Drug Disposition 11: 31–37, 1990CrossRefGoogle Scholar
  21. Ellinwood EH, Heatherly DG, Nikaido AM, Bjornsson TD, Kilts C. Comparative pharmacokinetics and pharmacodynamics or lorazepam, alprazolam and diazepam. Psychopharmacology 86: 392–399, 1985PubMedCrossRefGoogle Scholar
  22. Ellinwood EH, Nikaido AM, Heatherly DG, Bjornsson TD. Benzodiazepine pharmacodynamics: evidence for biophase rate limiting mechanisms. Psychopharmacology 91: 168–174, 1987PubMedCrossRefGoogle Scholar
  23. Fawcett JA, Kravitz HM. Alprazolam: pharmacokinetics, clinical efficacy, and mechanism of action. Pharmacotherapy 2: 243–254, 1982PubMedGoogle Scholar
  24. Fleishaker JC, Hulst LK. Effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of alprazolam in healthy volunteers. Pharmaceutical Research 9: 294, 1992CrossRefGoogle Scholar
  25. Fleishaker JC, Phillips JP, Eller MG, Smith RB. Pharmacokinetics and pharmacodynamics of alprazolam following single and multiple oral doses of a sustained-release formulation. Journal of Clinical Pharmacology 29: 543–549, 1989PubMedGoogle Scholar
  26. Fraser AD. Urinary screening for alprazolam, triazolam, and their metabolites with the EMIT® d.a.u.™ benzodiazepine metabolite assay. Journal of Analytical Toxicology 11: 263–266, 1987PubMedGoogle Scholar
  27. Fraser AD, Bryan W, Isner AF. Urinary screening for alprazolam and its major metabolites by the Abbott ADx and TDx analyzers with confirmation by GC/MS. Journal of Analytical Toxicology 15: 25–29, 1991PubMedGoogle Scholar
  28. Friedman H, Redmond DE, Greenblatt DJ. Comparative pharmacokinetics of alprazolam and lorazepam in humans and in African green monkeys. Psychopharmacology 104: 103–105, 1991PubMedCrossRefGoogle Scholar
  29. Grasela TH, Antal EJ, Ereshefsky L, Wells BG, Evans RL, et al. An evaluation of population pharmacokinetics in therapeutic trials. Part II. Detection of a drug-drug interaction. Clinical Pharmacology and Therapeutics 42: 433–441, 1987PubMedCrossRefGoogle Scholar
  30. Greenblatt DJ, Divoll M, Abernethy DR, Moschitto LJ, Smith RB, et al. Alprazolam kinetics in the elderly: relation to antipyrine disposition. Archives of General Psychiatry 40: 287–290, 1983aPubMedCrossRefGoogle Scholar
  31. Greenblatt DJ, Divoll M, Moschitto LJ, Shader RI. Electron-capture gas chromatographic analysis of the triazolobenzodiazepines alprazolam and triazolam. Journal of Chromatography 225: 202–207, 1981PubMedCrossRefGoogle Scholar
  32. Greenblatt DJ, Divoll M, Shader RI. Automated gas chromatographic determination of plasma alprazolam concentrations. Journal of Clinical Psychopharmacology 3: 366–368, 1983bPubMedGoogle Scholar
  33. Greenblatt DJ, Harmatz JS, Dorsey C, Shader RI. Comparative single-dose kinetics and dynamics of lorazepam, alprazolam, prazepam, and placebo. Clinical Pharmacology and Therapeutics 44: 326–334, 1988PubMedCrossRefGoogle Scholar
  34. Greenblatt DJ, Harmatz JS, Friedman H, Locniskar A, Shader RI. A large-sample study of diazepam pharmacokinetics. Therapeutic Drug Monitoring 11: 652–657, 1989PubMedCrossRefGoogle Scholar
  35. Greenblatt DJ, Harmatz JS, Shader RI. Clinical pharmacokinetics of anxiolytics and hypnotics in the elderly: therapeutic considerations. Clinical Pharmacokinetics 21: 165–177, 262-273, 1991PubMedCrossRefGoogle Scholar
  36. Greenblatt DJ, Harmatz JS, Shader RI. Plasma alprazolam concentrations: relation to efficacy and side effects in panic disorder. Archives of General Psychiatry, in press, 1993Google Scholar
  37. Greenblatt DJ, Javaid JI, Locniskar A, Harmatz JS, Shader RI. Gas chromatographic analysis of alprazolam in plasma: replicability, stability and specificity. Journal of Chromatography 534: 202–207, 1990aPubMedCrossRefGoogle Scholar
  38. Greenblatt DJ, Miller LG, Shader RI. Benzodiazepine discontinuation syndromes. Journal of Psychiatric Research 24 (Suppl. 2): 73–79, 1990bPubMedCrossRefGoogle Scholar
  39. Greenblatt DJ, Preskorn SH, Cotreau MM, Horst WD, Harmatz JS. Fluoxetine impairs clearance of alprazolam but not of clonazepam. Clinical Pharmacology and Therapeutics 52: 479–486, 1992bPubMedCrossRefGoogle Scholar
  40. Greenblatt DJ, Shader RI. Pharmacokinetics of antianxiety agents. In Meitzer HY (Ed.) Psychopharmacology: the third generation of progress, pp. 1377–1386, Raven Press, New York, 1987Google Scholar
  41. Greenblatt DJ, Shader RI. Say ‘no’ to drug testing. Journal of Clinical Psychopharmacology 10: 157–159, 1990PubMedCrossRefGoogle Scholar
  42. Javaid JI, Liskevych U. Quantitative analysis of alprazolam in human plasma by combined capillary gas chromatography/negative ion chemical ionization mass spectrometry. Biomedical and Environmental Mass Spectrometry 13: 129–132, 1986PubMedCrossRefGoogle Scholar
  43. Joern WA, Joern AB. Detection of alprazolam (Xanax) and its metabolites in urine using dual capillary column, dual nitrogen detector gas chromatography. Journal of Analytical Toxicology 11: 247–251, 1987PubMedGoogle Scholar
  44. Juhl RP, van Thiel DH, Dittert LW, Smith RB. Alprazolam pharmacokinetics in alcoholic liver disease. Journal of Clinical Pharmacology 24: 113–119, 1984PubMedGoogle Scholar
  45. Kirkwood C, Moore A, Hayes P, DeVane CL, Pelonero A. Influence of menstrual cycle and gender on alprazolam pharmacokinetics. Clinical Pharmacology and Therapeutics 50: 404–209, 1991PubMedCrossRefGoogle Scholar
  46. Kristjánsson F, Thorsteinsson SB. Disposition of alprazolam in human volunteers. Differences between genders. Acta Pharmaceutica Nordica 3: 249–250, 1991PubMedGoogle Scholar
  47. Kroboth PD, McAuley JW, Smith RB. Alprazolam in the elderly: pharmacokinetics and pharmacodynamics during multiple dosing. Psychopharmacology 100: 477–484, 1990PubMedCrossRefGoogle Scholar
  48. Kroboth PD, Smith RB, Erb RJ. Tolerance to alprazolam after intravenous bolus and continuous infusion: psychomotor and EEG effects. Clinical Pharmacology and Therapeutics 43: 270–277, 1988PubMedCrossRefGoogle Scholar
  49. Kroboth PD, Smith RB, Sorkin MI, Silver MR, Rault R, et al. Triazolam protein binding and correlation with alpha-1 acid glycoprotein concentration. Clinical Pharmacology and Therapeutics 36: 379–383, 1984PubMedCrossRefGoogle Scholar
  50. Kronbach T, Mathys D, Umeno M, Gonzalez FJ, Meyer UA. Oxidation of midazolam and triazolam by human liver cytochrome P450 III A4. Molecular Pharmacology 36: 89–96, 1989PubMedGoogle Scholar
  51. Lasher TA, Fleishaker JC, Steenwyk RC, Antal EJ. Pharmacokinetic pharmacodynamic evaluation of the combined administration of alprazolam and fluoxetine. Psychopharmacology 104: 323–327, 1991PubMedCrossRefGoogle Scholar
  52. Lesser IM, Lydiard RB, Antal E, Rubin RT, Ballenger JC, et al. alprazolam plasma concentrations and treatment response in panic disorder and agoraphobia. American Journal of Psychiatry 149: 1556–1562, 1992PubMedGoogle Scholar
  53. Lillsunde P, Seppala T. Simultaneous screening and quantitative analysis of benzodiazepines by dual-channel gas chromatography using electron-capture and nitrogen-phosphorus detection. Journal of Chromatography 533: 97–110, 1990PubMedCrossRefGoogle Scholar
  54. Lin K-M, Lau JK, Smith R, Phillips P, Antal E, Poland RE. Comparison of alprazolam plasma levels in normal Asian and Caucasian male volunteers. Psychopharmacology 96: 365–369, 1988PubMedCrossRefGoogle Scholar
  55. Linnoila M, Stapleton JM, Lister R, Moss H, Lane E, et al. Effects of single doses of alprazolam and diazepam, alone and in combination with ethanol, on psychomotor and cognitive performance and on autonomic nervous system reactivity in healthy volunteers. European Journal of Clinical Pharmacology 39: 21–28, 1990PubMedCrossRefGoogle Scholar
  56. Lopez F, Miller LG, Greenblatt DJ, Chesley S, Schatzki A, et al. Chronic administration of benzodiazepines-V. Rapid onset of behavioral and neurochemical alterations after discontinuation of alprazolam. Neuropharmacology 29: 237–241, 1990PubMedCrossRefGoogle Scholar
  57. Lopez F, Miller LG, Greenblatt DJ, Paul SM, Shader RI. Low-dose alprazolam augments motor activity in mice. Pharmacology Biochemistry & Behavior 30: 511–513, 1988CrossRefGoogle Scholar
  58. McCabe RT, Mahan DR, Smith RB, Wamsley JK. Characterization of [3H] alprazolam binding to central benzodiazepine receptors. Pharmacology Biochemistry & Behavior 37: 365–370, 1990CrossRefGoogle Scholar
  59. McCormick SR, Neilsen J, Jatlow P. Quantification of alprazolam in serum or plasma by liquid chromatography. Clinical Chemistry 30: 1652–1655, 1984PubMedGoogle Scholar
  60. Miller LG. Chronic benzodiazepine administration: from the patient to the gene. Journal of Clinical Pharmacology 31: 492–495, 1991PubMedGoogle Scholar
  61. Miller LG, Greenblatt DJ, Barnhill JG, Deutsch SI, Shader RI, et al. Benzodiazepine receptor binding of triazolobenzodiazepines in vivo: increased receptor number with low-dose alprazolam. Journal of Neurochemistry 49: 1595–1601, 1987PubMedCrossRefGoogle Scholar
  62. Miller LG, Woolverton S, Greenblatt DJ, Lopez F, Roy RB, et al. Chronic benzodiazepine administration. IV. Rapid development of tolerance and receptor downregulation associated with alprazolam administration. Biochemical Pharmacology 38: 3773–3777, 1989PubMedCrossRefGoogle Scholar
  63. Miller RL, DeVane CL. Alprazolam, α-hydroxy- and 4-hydroxyalprazolam analysis in plasma by high-performance liquid chromatography. Journal of Chromatography 430: 180–186, 1988PubMedCrossRefGoogle Scholar
  64. Moschitto LJ, Greenblatt DJ. Concentration-independent plasma protein binding of benzodiazepines. Journal of Pharmacy and Pharmacology 35: 179–180, 1983PubMedCrossRefGoogle Scholar
  65. Norman TR, Burrows GD, McIntyre IM. Pharmacokinetic and pharmacodynamic effects of a single nocturnal dose of alprazolam. International Clinical Psychopharmacology 5: 111–117, 1990PubMedCrossRefGoogle Scholar
  66. Ochs HR, Greenblatt DJ, Labedzki L, Smith RB. Alprazolam kinetics in patients with renal insufficiency. Journal of Clinical Psychopharmacology 6: 292–294, 1986PubMedCrossRefGoogle Scholar
  67. Ochs HR, Greenblatt DJ, Verburg-Ochs B. Effect of alprazolam on digoxin kinetics and creatinine clearance. Clinical Pharmacology and Therapeutics 38: 595–598, 1985PubMedCrossRefGoogle Scholar
  68. Ochs HR, Greenblatt DJ, Verburg-Ochs B. Propranolol interactions with diazepam, lorazepam, and alprazolam. Clinical Pharmacology and Therapeutics 36: 451–455, 1984PubMedCrossRefGoogle Scholar
  69. Pourbaix S, Desager JP, Hulhoven R, Smith RB, Harvengt C. Pharmacokinetic consequences of long term coadministration of Cimetidine and triazolobenzodiazepines, alprazolam and triazolam, in healthy subjects. International Journal of Clinical Pharmacology, Therapy and Toxicology 23: 447–451, 1985Google Scholar
  70. Richelson E, Nelson A, Neeper R. Binding of benzodiazepines and some major metabolites at their sites in normal human frontal cortex in vitro. Journal of Pharmacology and Experimental Therapeutics 256: 897–901, 1991PubMedGoogle Scholar
  71. Rickeis K, Schweizer E, Case G, Greenblatt DJ. Long-term therapeutic use of benzodiazepines. I. Effects of abrupt discontinuation. Archives of General Psychiatry 47: 899–907, 1990CrossRefGoogle Scholar
  72. Scavone JM, Blyden GT, Greenblatt DJ. Lack of effect of influenza vaccine on the pharmacokinetics of antipyrine, alprazolam, paracetamol (acetaminophen) and lorazepam. Clinical Pharmacokinetics 16: 180–185, 1989PubMedCrossRefGoogle Scholar
  73. Scavone JM, Greenblatt DJ, Goddard JE, Friedman H, Harmatz JS, Shader RI. The pharmacokinetics and pharmacodynamics of sublingual and oral alprazolam in the post-prandial state. European Journal of Clinical Pharmacology 42: 439–443, 1992PubMedGoogle Scholar
  74. Scavone JM, Greenblatt DJ, Locniskar A, Shader RI. Alprazolam pharmacokinetics in women on low-dose oral contraceptives. Journal of Clinical Pharmacology 28: 454–457, 1988PubMedGoogle Scholar
  75. Scavone JM, Greenblatt DJ, Shader RI. Alprazolam kinetics following sublingual and oral administration. Journal of Clinical Psychopharmacology 7: 332–334, 1987PubMedCrossRefGoogle Scholar
  76. Schmith VD, Cox SR, Zemaitis MA, Kroboth PD. New high-performance liquid chromatographic method for the determination of alprazolam and its metabolites in serum: instability of 4-hydroxyalprazolam. Journal of Chromatography 568: 253–260, 1991aPubMedCrossRefGoogle Scholar
  77. Schmith VD, Piraino B, Smith RB, Kroboth PD. Alprazolam in end-stage renal disease: I. Pharmacokinetics. Journal of Clinical Pharmacology 31: 571–579, 1991bPubMedGoogle Scholar
  78. Schmith VD, Piraino B, Smith RB, Kroboth PD. Alprazolam in end-stage renal disease. II. Pharmacodynamics. Clinical Pharmacology and Therapeutics 51: 533–540, 1992PubMedCrossRefGoogle Scholar
  79. Schweizer E, Rickeis K, Case WG, Greenblatt DJ. Long-term therapeutic use of benzodiazepines. II. Effects of gradual taper. Archives of General Psychiatry 47: 908–915, 1990PubMedCrossRefGoogle Scholar
  80. Sethy VH, Harris DW. Determination of biological activity of alprazolam, triazolam and their metabolites. Journal of Pharmacy and Pharmacology 34: 115–116, 1982PubMedCrossRefGoogle Scholar
  81. Sethy VH, Russell RR, Daenzer CL. Interaction of triazolobenzodiazepines with benzodiazepine receptors. Journal of Pharmacy and Pharmacology 35: 524–526, 1983PubMedCrossRefGoogle Scholar
  82. Smith RB, Gwilt PR, Wright CE. Single- and multiple-dose pharmacokinetics of oral alprazolam in healthy smoking and nonsmoking men. Clinical Pharmacy 2: 139–143, 1983PubMedGoogle Scholar
  83. Smith RB, Kroboth PD. Influence of dosing regimen on alprazolam and metabolite serum concentrations and tolerance to sedative and psychomotor effects. Psychopharmacology 93: 105–112, 1987PubMedCrossRefGoogle Scholar
  84. Smith RB, Kroboth PD, Vanderlugt JT, Phillips JP, Juhl RP. Pharmacokinetics and pharmacodynamics of alprazolam after oral and IV administration. Psychopharmacology 84: 452–456, 1984PubMedCrossRefGoogle Scholar
  85. Stoehr GP, Kroboth PD, Juhl RP, Wender DB, Phillips JP, et al. Effect of oral contraceptives on triazolam, temazepam, alprazolam, and lorazepam kinetics. Clinical Pharmacology and Therapeutics 36: 683–690, 1984PubMedCrossRefGoogle Scholar
  86. Tollefson G, Lesar T, Grothe D, Garvey M. Alprazolam-related digoxin toxicity. American Journal of Psychiatry 141: 1612–1614, 1984PubMedGoogle Scholar
  87. von Moltke L, Greenblatt DJ, Harmatz JS, Shader RI. In vitro metabolism of alprazolam in multiple species. Abstract. Clinical Pharmacology and Therapeutics 53: 199, 1993Google Scholar
  88. Wincor MZ, Munjack DJ, Palmer R. Alprazolam levels and response in panic disorder: preliminary results. Journal of Clinical Psychopharmacology 11: 48–51, 1991PubMedCrossRefGoogle Scholar
  89. Wright CE, Chambers JH. Influence of alprazolam input rate and steady-state pharmacokinetics on psychomotor performance in healthy subjects. Pharmaceutical Research 8: 250, 1991Google Scholar
  90. Wright CE, Fleishaker JC, Lasher TA. Pharmacokinetics and psychomotor responses in healthy subjects receiving alprazolam. Pharmacotherapy 10: 256, 1990Google Scholar
  91. Wright CE, McNamara PJ. Characterization of the protein binding of triazolam and alprazolam. Pharmaceutical Research 6: 239, 1989CrossRefGoogle Scholar

Copyright information

© Adis International Limited 1993

Authors and Affiliations

  • David J. Greenblatt
    • 1
    • 2
  • C. Eugene Wright
    • 3
  1. 1.Department of Pharmacology and Experimental TherapeuticsTufts University School of MedicineBostonUSA
  2. 2.Division of Clinical PharmacologyNew England Medical Center HospitalBostonUSA
  3. 3.Clinical Pharmacokinetics UnitThe Upjohn CompanyKalamazooUSA

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