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British Journal of Pharmacology and Chemotherapy logoLink to British Journal of Pharmacology and Chemotherapy
. 1963 Apr;20(2):285–298. doi: 10.1111/j.1476-5381.1963.tb01468.x

The excretion of pethidine and its derivatives

A M Asatoor, D R London, M D Milne, M L Simenhoff
PMCID: PMC1703639  PMID: 13965101

Abstract

The excretion of pethidine and its metabolite norpethidine is increased in acid urine and decreased in alkaline urine. Excretion of these two bases is the main route of removal of pethidine from the body if the urine is highly acid. If the urine is alkaline, excretion of the hydrolysis products meperidinic and normeperidinic acids, both as free acids and as conjugates, is the more important means of elimination of the drug. Acidification of the urine with ammonium chloride is indicated in the therapy of cases of pethidine poisoning in patients with reduced metabolic breakdown of the drug by the microsomal enzyme systems within liver cells. Reversed-phase chromatography of the dinitrophenyl derivative of norpethidine may prove to be of forensic importance in the diagnosis of pethidine poisoning or of pethidine addiction. Norpethidine can be detected in the urine by this method for at least 3 days after the last dose of pethidine. Analytical sensitivity is increased by acidification of the urine which produces a temporary rise of the excretion rate.

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Selected References

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  1. ASATOOR A. M., KERR D. N. Amines in blood and urine in relation to liver disease. Clin Chim Acta. 1961 Mar;6:149–156. doi: 10.1016/0009-8981(61)90078-x. [DOI] [PubMed] [Google Scholar]
  2. BAER J. E., BEYER K. H., PAULSON S. F., RUSSO H. F. Renal elimination of 3-methylaminoisocamphane hydrochloride (mecamylamine). Am J Physiol. 1956 Jul;186(1):180–186. doi: 10.1152/ajplegacy.1956.186.1.180. [DOI] [PubMed] [Google Scholar]
  3. BATTERMAN R. C., SOMMER E. M. Fate of gentisic acid in man as influenced by alkalinization and acidification. Proc Soc Exp Biol Med. 1953 Mar;82(3):376–379. doi: 10.3181/00379727-82-20121. [DOI] [PubMed] [Google Scholar]
  4. BURNS J. J., BERGER B. L., LIEF P. A., WOLLACK A., PAPPER E. M., BRODIE B. B. The physiological disposition and fate of meperidine (demerol) in man and a method for its estimation in plasma. J Pharmacol Exp Ther. 1955 Jul;114(3):289–298. [PubMed] [Google Scholar]
  5. DUNDEE J. W., TINCKLER L. F. Pethidine and liver damage. Br Med J. 1952 Sep 27;2(4786):703–704. doi: 10.1136/bmj.2.4786.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. ELIOTT H. W., PLOTNIKOFF N. P., WAY E. L. Biotransformation products of meperidine excreted in the urine of man. J Pharmacol Exp Ther. 1956 Aug;117(4):414–419. [PubMed] [Google Scholar]
  7. FOUTS J. R., BRODIE B. B. On the mechanism of drug potentiation by iproniazid (2-isopropyl-1-isonicotinyl hydrazine). J Pharmacol Exp Ther. 1956 Apr;116(4):480–485. [PubMed] [Google Scholar]
  8. GUTMAN A. B., DAYTON P. G., YU T. F., BERGER L., CHEN W., SICAM L. E., BURNS J. J. A study of the inverse relationship between pKa and rate of renal excretion of phenylbutazone analogs in man and dog. Am J Med. 1960 Dec;29:1017–1033. doi: 10.1016/0002-9343(60)90082-6. [DOI] [PubMed] [Google Scholar]
  9. GUTMAN A., YU T. F., SIROTA J. H. A study, by simultaneous clearance techniques, of salicylate excretion in man: effect of alkalinization of the urine by bicarbonate administration; effect of probenecid. J Clin Invest. 1955 May;34(5):711–721. doi: 10.1172/JCI103124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. HARINGTON M., KINCAID-SMITH P., MILNE M. D. Pharmacology and clinical use of pempidine in the treatment of hypertension. Lancet. 1958 Jul 5;2(7036):6–11. doi: 10.1016/s0140-6736(58)90002-3. [DOI] [PubMed] [Google Scholar]
  11. Jailer J. W., Rosenfeld M., Shannon J. A. THE INFLUENCE OF ORALLY ADMINISTERED ALKALI AND ACID ON THE RENAL EXCRETION OF QUINACRINE, CHLOROQUINE AND SANTOQUINE. J Clin Invest. 1947 Nov;26(6):1168–1172. doi: 10.1172/JCI101909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. MILNE M. D., CRAWFORD M. A., GIRAO C. B., LOUGHRIDGE L. The excretion of indolylacetic acid and related indolic acids in man and the rat. Clin Sci. 1960 Feb;19:165–179. [PubMed] [Google Scholar]
  13. MILNE M. D., ROWE G. G., SOMERS K., MUEHRCKE R. C., CRAWFORD M. A. Observations on the pharmacology of mecamylamine. Clin Sci. 1957 Nov;16(4):599–614. [PubMed] [Google Scholar]
  14. MILNE M. D., SCRIBNER B. H., CRAWFORD M. A. Non-ionic diffusion and the excretion of weak acids and bases. Am J Med. 1958 May;24(5):709–729. doi: 10.1016/0002-9343(58)90376-0. [DOI] [PubMed] [Google Scholar]
  15. MITCHELL R. S. Fatal toxic encephalitis occurring during iproniazid therapy in pulmonary tuberculosis. Ann Intern Med. 1955 Feb;42(2):417–424. doi: 10.7326/0003-4819-42-2-417. [DOI] [PubMed] [Google Scholar]
  16. Milne M. D., Asatoor A. M., Edwards K. D., Loughridge L. W. The intestinal absorption defect in cystinuria. Gut. 1961 Dec;2(4):323–337. doi: 10.1136/gut.2.4.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. ORLOFF J., BERLINER R. W. The mechanism of the excretion of ammonia in the dog. J Clin Invest. 1956 Feb;35(2):223–235. doi: 10.1172/JCI103267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. PAPP C., BENAIM S. Toxic effects of iproniazid in a patient with angina. Br Med J. 1958 Nov 1;2(5104):1070–1072. doi: 10.1136/bmj.2.5104.1070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. PLOTNIKOFF N. P., ELLIOTT H. W., WAY E. L. The metabolism of N-C14H3 labeled meperidine. J Pharmacol Exp Ther. 1952 Apr;104(4):377–386. [PubMed] [Google Scholar]
  20. SANDLER M., SPECTOR R. G. Effect of urinary pH on 5-hydroxytryptamine excretion in the rat. Nature. 1961 Mar 11;189:838–840. doi: 10.1038/189838a0. [DOI] [PubMed] [Google Scholar]
  21. SHEE J. C. Dangerous potentiation of pethidine by iproniazid, and its treatment. Br Med J. 1960 Aug 13;2(5197):507–509. doi: 10.1136/bmj.2.5197.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. TERP P. Studies on elimination of procaine. III. Determination of the renal clearance of procaine and p-amino-benzoic acid in dog and rabbit. Acta Pharmacol Toxicol (Copenh) 1951;7(3):259–280. doi: 10.1111/j.1600-0773.1951.tb02868.x. [DOI] [PubMed] [Google Scholar]
  23. TORRETTI J., WEINER I. M., MUDGE G. H. Renal tubular secretion and reabsorption of organic bases in the dog. J Clin Invest. 1962 Apr;41:793–804. doi: 10.1172/JCI104537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. WADDELL W. J., BUTLER T. C. Renal excretion of 5,5-dimethyl-2-4-oxazolidinedione (product of demethylation of trimethadione. Proc Soc Exp Biol Med. 1957 Dec;96(3):563–565. doi: 10.3181/00379727-96-23540. [DOI] [PubMed] [Google Scholar]
  25. WADDELL W. J., BUTLER T. C. The distribution and excretion of phenobarbital. J Clin Invest. 1957 Aug;36(8):1217–1226. doi: 10.1172/JCI103518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. WEINER I. M., WASHINGTON J. A., 2nd, MUDGE G. H. On the mechanism of action of probenecid on renal tubular secretion. Bull Johns Hopkins Hosp. 1960 Jun;106:333–346. [PubMed] [Google Scholar]
  27. WEINER I. M., WASHINGTON J. A., 2nd, MUDGE G. H. Studies on the renal excretion of salicylate in the dog. Bull Johns Hopkins Hosp. 1959 Nov;105:284–297. [PubMed] [Google Scholar]
  28. WOODRUFF M. W., MALVIN R. L., THOMPSON I. M. The renal transport of nitrofurantoin. Effect of acid-base balance upon its excretion. JAMA. 1961 Apr 1;175:1132–1135. doi: 10.1001/jama.1961.03040130016004. [DOI] [PubMed] [Google Scholar]

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