Summary
The clearance of the antipyretic-analgesic drug acetaminophen, biotransformed in humans by glucuronide and sulfate conjugation, was evaluated in 32 healthy young and elderly volunteers. Subjects received a single 650-mg dose of acetaminophen, and multiple plasma concentrations measured over the next 12 h. Random subgroups of subjects also participated in studies of the oxidized benzodiazepines diazepam, desmethyldiazepam and alprazolam, and of the conjugated benzodiazepines lorazepam, oxazepam and temazepam. Acetaminophen clearance was not related to that of the oxidized benzodiazepines, but was highly correlated with clearance of lorazepam (r=0.70, n=11, p<0.02), oxazepam (r=0.76, n=14, p<0.005) and temazepam (r=0.63, n=16, p<0.01). Thus acetaminophen may serve as a probe or marker compound to evaluate drug conjugating capacity in humans.
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References
Vesell ES (1979) The antipyrine test in clinical pharmacology. Conceptions and misconceptions. Clin Pharmacol Ther 26: 275–86
Stevenson IH (1977) Factors influencing antipyrine elimination. Br J Clin Pharmacol 4: 261–5
Greenblatt DJ, Divoll M, Abernethy DR, Harmatz JS, Shader RI (1982) Antipyrine kinetics in the elderly: Prediction of age-related changes in benzodiazepine oxidizing capacity. J Pharmacol Exper Ther 220: 120–6
Greenblatt DJ, Divoll M, Abernethy DR, Moschitto LJ, Smith RB, Shader RI (1983) Alprazolam kinetics in the elderly: Relation to antipyrine disposition. Arch Gen Psychiatry 40: 281–290
Forrest JAH, Clements JA, Prescott LF (1982) Clinical pharmacokinetics of paracetamol. Clin Pharmacokinet 7: 93–107
Divoll M, Abernethy DR, Ameer B, Greenblatt DJ (1982) Acetaminophen kinetics in the elderly. Clin Pharmacol Ther 31: 151–6
Ameer B, Greenblatt DJ, Divoll M, Abernethy DR, Shargel L (1981) High performance liquid chromatographic determination of acetaminophen in plasma: Single dose pharmacokinetics studies. J Chromatogr 226: 224–30
Greenblatt DJ, Allen MD, Harmatz JS, Shader RI (1980) Diazepam disposition determinants. Clin Pharmacol Ther 27: 301–12
Allen MD, Greenblatt DJ, Harmatz JS, Shader RI (1980) Desmethyldiazepam kinetics in the elderly after oral prazepam. Clin Pharmacol Ther 28: 196–202
Shader RI, Greenblatt DJ, Ciraulo DA, Divoll M, Harmatz JS, Georgotas A (1981) Effect of age and sex on disposition of desmethyldiazepam formed from its precursor clorazepate. Psychopharmacology 1981; 75: 1193–7
Greenblatt DJ, Divoll M, Harmatz JS, Shader RI (1980) Oxazepam kinetics: Effects of age and sex. J Pharmacol Exper Ther 215: 86–91
Greenblatt DJ, Allen MD, Locniskar A, Harmaatz JS, Shader RI (1979) Lorazepam kinetics in the elderly. Clin Pharmacol Ther 26: 103–13
Divoll M, Greenblatt DJ, Harmatz JS, Shader RJ (1981) Effect of age and gender on disposition of temazepam. J Pharm Sci 70: 1104–7
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Greenblatt, D.J., Abernethy, D.R., Divoll, M. et al. Close correlation of acetaminophen clearance with that of conjugated benzodiazepines but not oxidized benzodiazepines. Eur J Clin Pharmacol 25, 113–115 (1983). https://doi.org/10.1007/BF00544026
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DOI: https://doi.org/10.1007/BF00544026