Influence of ammonium chloride on the tissue distribution of anticholinergic drugs in rats

Junko Ishizaki, Koichi Yokogawa, Emi Nakashima, Shoji Ohkuma, Fujio Ichimura

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Ammonium chloride (NH4Cl) increases lysosomal pH and thereby abolishes intralysosomal accumulation of drugs. Its effect on the tissue distribution of biperiden and trihexyphenidyl in rats has been investigated. The tissue-plasma concentration ratios (K(p)) of these drugs in various tissues were determined by infusion studies at steady-state in the presence or absence of NH4Cl. Treatment with NH4Cl reduced the K(p) values for both drugs, causing the largest reduction in K(p) in the lung (52.1 to 11.8 for biperiden and 59.5 to 18.9 for trihexyphenidyl; ratios of decrease 0.77 and 0.68, respectively), followed by the heart and kidneys, with relatively small reductions in the brain, gut, muscle and fat. Subcellular fractionation studies in the lung indicated that the subcellular fraction-plasma concentration ratio of each drug at the steady state (K(p,sf)) was reduced by treatment with NH4Cl, with the largest decrease in the post-nuclear fraction (ratio of decrease 0.82 for biperiden and 0.74 for trihexyphenidyl), followed by the nucleus, microsomes and supernatant, in that order. A strong correlation was found between the ratio of decrease in K(p,sf) after NH4Cl treatment and the specific activity of acid phosphatases, a marker of lysosomes, in each fraction (biperiden, r = 0.948; trihexyphenidyl, r = 0.945). These results suggest that acidic organelles contribute significantly to the distribution kinetics of anticholinergic drugs.

Original languageEnglish
Pages (from-to)761-766
Number of pages6
JournalJournal of Pharmacy and Pharmacology
Volume50
Issue number7
Publication statusPublished - 1998 Jul

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Biperiden
Trihexyphenidyl
Ammonium Chloride
Cholinergic Antagonists
Tissue Distribution
Pharmaceutical Preparations
Lung
Subcellular Fractions
Acid Phosphatase
Microsomes
Lysosomes
Organelles
Pharmacokinetics
Fats
Kidney
Muscles
Brain

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Ishizaki, J., Yokogawa, K., Nakashima, E., Ohkuma, S., & Ichimura, F. (1998). Influence of ammonium chloride on the tissue distribution of anticholinergic drugs in rats. Journal of Pharmacy and Pharmacology, 50(7), 761-766.

Influence of ammonium chloride on the tissue distribution of anticholinergic drugs in rats. / Ishizaki, Junko; Yokogawa, Koichi; Nakashima, Emi; Ohkuma, Shoji; Ichimura, Fujio.

In: Journal of Pharmacy and Pharmacology, Vol. 50, No. 7, 07.1998, p. 761-766.

Research output: Contribution to journalArticle

Ishizaki, J, Yokogawa, K, Nakashima, E, Ohkuma, S & Ichimura, F 1998, 'Influence of ammonium chloride on the tissue distribution of anticholinergic drugs in rats', Journal of Pharmacy and Pharmacology, vol. 50, no. 7, pp. 761-766.
Ishizaki J, Yokogawa K, Nakashima E, Ohkuma S, Ichimura F. Influence of ammonium chloride on the tissue distribution of anticholinergic drugs in rats. Journal of Pharmacy and Pharmacology. 1998 Jul;50(7):761-766.
Ishizaki, Junko ; Yokogawa, Koichi ; Nakashima, Emi ; Ohkuma, Shoji ; Ichimura, Fujio. / Influence of ammonium chloride on the tissue distribution of anticholinergic drugs in rats. In: Journal of Pharmacy and Pharmacology. 1998 ; Vol. 50, No. 7. pp. 761-766.
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