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  • Title: Pharmacokinetics of amitriptyline influenced by oral charcoal and urine pH.
    Author: Kärkkäinen S, Neuvonen PJ.
    Journal: Int J Clin Pharmacol Ther Toxicol; 1986 Jun; 24(6):326-32. PubMed ID: 3015809.
    Abstract:
    The effects of orally given activated charcoal, sodium bicarbonate and ammonium chloride on the pharmacokinetics of amitriptyline were studied in 6 volunteers in a randomized, cross-over study. The serum and urine concentrations of amitriptyline and nortriptyline were determined by HPLC for up to 72 h. Activated charcoal (50 g), given within 5 min of the amitriptyline hydrochloride dose (75 mg), reduced its absorption by 99%. When given in repeated doses from 6 h on, 50 g followed by 12.5 g at 6-h intervals, charcoal shortened the serum half-life of amitriptyline by 20% and that of nortriptyline by 35% (p less than 0.05). The renal excretions of amitriptyline and nortriptyline increased 1000-fold by the acidification of urine pH to 4. However, the cumulative excretion of amitriptyline and nortriptyline even into acidic urine only accounted for up to 5% of the dose during 72 h. Since urinary pH has a great influence on the ratio of urinary versus serum amitriptyline and nortriptyline concentrations, pH should be taken into consideration, when the clinical significance of their concentrations in urine is evaluated. Activated charcoal in adequate doses very effectively prevents the absorption of that fraction of amitriptyline which is in the stomach at the time of charcoal administration. Furthermore, given in repeated oral doses, charcoal increases, to some extent, the rate of elimination of amitriptyline and nortriptyline, probably by interrupting their enterohepatic or enteroenteric circulation.
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