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Clearance of the Antihistamine Doxylamine

Reduced in Elderly Men But Not in Elderly Women

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Summary

A single oral dose of doxylamine succinate 25mg was administered to 21 young (20 to 43 years) and 22 elderly (60 to 87 years) volunteers. Multiple plasma doxylamine concentrations were determined during a 30-hour period after each dose. Elderly and young women did not differ significantly in peak plasma doxylamine concentration ( C max ) [116 vs 103 µg/L], time to C max ( t max ) [2.4 vs 2.4h], elimination half-life (12.2 vs 10.1h), volume of distribution (179 vs 176L) or clearance (191 vs 218 ml/min). C max (107 vs 108 µg/L) and t max (2.1 vs 1.6h) also did not differ between elderly and young men. However, elderly men had reduced doxylamine clearance (174 vs 240 ml/min, p < 0.02; 2.5 vs 3.2 ml/min/kg, p < 0.07) and prolonged half-life (15.5 vs 10.2h, p < 0.05). The reduced doxylamine clearance and prolonged half-life in elderly men, but not in elderly women, is similar to results for many other drugs which are transformed by oxidation.

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References

  • Abernethy DR, Greenblatt DJ. Pharmacokinetics of drugs in obesity. Clinical Pharmacokinetics 7: 108–124, 1982

    Article  PubMed  CAS  Google Scholar 

  • Abernethy DR, Greenblatt DJ. Impairment of lidocaine clearance in elderly male subjects. Journal of Cardiovascular Pharmacology 5: 1093–1096, 1983

    Article  PubMed  CAS  Google Scholar 

  • Friedman H, Greenblatt DJ. The pharmacokinetics of doxylamine: use of automated gas chromatography with nitrogen-phosphorus detection. Journal of Clinical Pharmacology 25: 448–451, 1985

    PubMed  CAS  Google Scholar 

  • Ganes DA, Hindmarsh KW, Midha KK. Doxylamine metabolism in rat and monkey. Xenobiotica 16: 781–794, 1986

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Abernethy DR, Locniskar A, Harmatz JS, Limjuco RA, et al. Effect of age, gender, and obesity on midazolam kinetics. Anesthesiology 61: 27–35, 1984a

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Abernethy DR, Matlis R, Harmatz JS, Shader RI. Absorption and disposition of ibuprofen in the elderly. Arthritis and Rheumatism 27: 1066–1069, 1984b

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Abernethy DR, Shader RI. Pharmacokinetic aspects of drug therapy in the elderly. Therapeutic Drug Monitoring 8: 249–255, 1986

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Allen MD, Harmatz JS, Shader RI. Diazepam disposition determinants. Clinical Pharmacology and Therapeutics 27: 301–312, 1980

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Divoll M, Abernethy DR, Harmatz JS, Shader RI. Antipyrine kinetics in the elderly: prediction of age-related changes in benzodiazepine oxidizing capacity. Journal of Pharmacology and Experimental Therapeutics 220: 120–126, 1982a

    PubMed  CAS  Google Scholar 

  • 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, 1983a

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Divoll M, Puri SK, Ho I, Zinny MA, et al. Clobazam kinetics in the elderly. British Journal of Pharmacology 12: 631–636, 1981

    Article  CAS  Google Scholar 

  • Greenblatt DJ, Divoll M, Puri SK, Ho I, Zinny MA, et al. Reduced single-dose clearance of clobazam in elderly men predicts increased multiple-dose accumulation. Clinical Pharmacokinetics 8: 83–94, 1983b

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Friedman H, Burstein ES, Scavone JM, Blyden GT, et al. Trazodone kinetics: effect of age, gender, and obesity. Clinical Pharmacology and Therapeutics 42: 193–200, 1987

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Koch-Weser J. Clinical pharmacokinetics. New England Journal of Medicine 293: 702–705, 964-970, 1985

    Article  Google Scholar 

  • Greenblatt DJ, Sellers EM, Shader RI. Drug disposition in old age. New England Journal of Medicine 306: 1081–1088, 1982b

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Shader RI. Nonprescription psychotropic drugs. In Jarvik (Ed.) Psychopharmacology in the practice of medicine, pp. 345–357, Appleton-Century-Crofts, New York, 1977

    Google Scholar 

  • Holder CL, Korfmacher WA, Rushing LG, Thompson HC, Slikker W, et al. Formation of artifactual metabolites of doxylamine following acid hydrolysis. Journal of Chromatography 419: 113–122, 1987

    Article  PubMed  CAS  Google Scholar 

  • Lamy PP. Over-the-counter medication: the drug interactions we overlook. Journal of the American Geriatrics Society 30 (November Suppl.): S69–S75, 1982

    PubMed  CAS  Google Scholar 

  • Paton DM, Webster DR. Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines). Clinical Pharmacokinetics 10: 477–497, 1985

    Article  PubMed  CAS  Google Scholar 

  • Pond SM, Tozer TN. First-pass elimination: basic concepts and clinical consequences. Clinical Pharmacokinetics 9: 1–25, 1984

    Article  PubMed  CAS  Google Scholar 

  • Rickels K, Ginsberg J, Morris RJ, Newman HM, Schiller HM, et al. Doxylamine succinate in insomniac family-practice patients: a double-blind study. Current Therapeutic Research 35: 532–540, 1984

    Google Scholar 

  • Schmucker DL. Aging and drug disposition: an update. Pharmacological Reviews 37: 133–148, 1985

    PubMed  CAS  Google Scholar 

  • Slikker W, Holder CL, Lipe GW, Korfmacher WA, Thompson HC, et al. Metabolism of 14C-labeled doxylamine succinate (Bendectin) in the Rhesus monkey (Macaca mulatta). Journal of Analytical Toxicology 10: 87–92, 1986

    PubMed  CAS  Google Scholar 

  • Vestal RE. Pharmacology and aging. Journal of the American Geriatrics Society 30: 191–200, 1982

    PubMed  CAS  Google Scholar 

  • Wilkinson GR. Clearance approaches in pharmacology. Pharmacological Reviews 39: 1–47, 1987

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Clinical Pharmacology, Departments of Psychiatry and Medicine, Tufts University School of Medicine and New England Medical Center, Boston, Massachusetts, USA

    H. Friedman,  David J. Greenblatt, Joseph M. Scavone, Ethan S. Burstein, Hermann R. Ochs, Jerold S. Harmatz & Richard I. Shader

  2. Medizinische Universitätsklinik, University of Bonn, Federal Republic of Germany

    H. Friedman,  David J. Greenblatt, Joseph M. Scavone, Ethan S. Burstein, Hermann R. Ochs, Jerold S. Harmatz & Richard I. Shader

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  1. H. Friedman
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  2. David J. Greenblatt
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  3. Joseph M. Scavone
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  4. Ethan S. Burstein
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  5. Hermann R. Ochs
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  6. Jerold S. Harmatz
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  7. Richard I. Shader
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Friedman, H., Greenblatt, D.J., Scavone, J.M. et al. Clearance of the Antihistamine Doxylamine. Clin-Pharmacokinet 16, 312–316 (1989). https://doi.org/10.2165/00003088-198916050-00003

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  • DOI: https://doi.org/10.2165/00003088-198916050-00003

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