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Metabolism and excretion of 3‐hydroxyphenyltrimethylammonium and neostigmine
Author(s) -
HUSAIN M. A.,
ROBERTS J. B.,
THOMAS B. H.,
WILSON A.
Publication year - 1969
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1969.tb07994.x
Subject(s) - glucuronide , urine , conjugate , excretion , chemistry , metabolite , metabolism , neostigmine , endocrinology , medicine , biochemistry , biology , mathematical analysis , mathematics
1 Carbon‐14 labelled 3‐hydroxyphenyltrimethylammonium (3‐OH PTMA), an active metabolite of neostigmine, has been given to rats by intramuscular injection and its excretion, distribution and metabolism have been studied. 2 A method is described for the separation and estimation of free and conjugated 3‐OH PTMA in urine and liver. 3 In the first hour, about 20% of a dose is excreted in the urine as free 3‐OH PTMA and thereafter the rate of excretion of glucuronide conjugate exceeds that of free 3‐OH PTMA. In 24 hr 76.8% of the dose is excreted in urine mainly as the conjugate. 4 The peak concentration of radioactivity in blood occurs within 30 min and in liver within 1 hr after administration. More than 90% of the radioactivity in liver occurs as the glucuronide conjugate. Relatively high concentrations of radioactivity were found in liver and heart. 5 In the hen 3‐OH PTMA is rapidly excreted by renal tubular secretion. 6 Experiments with carbon‐14 labelled neostigmine show that up to 1 hr mainly unchanged neostigmine is excreted in urine; thereafter increasing amounts of free 3‐OH PTMA and its glucuronide conjugate are excreted. 7 It is concluded that the duration of action of neostigmine is determined by its rapid renal excretion and by its metabolism to the glucuronide conjugate of 3‐OH PTMA.