The kinetics of methaemoglobin production by orally administered p-aminopropiophenone (PAPP) was studied by using a kinetic model previously developed to describe methaemoglobinaemia consequent on intravenous injection of PAPP. Both ISIS, a simulation package, and NONLIN, a non-linear least-squares regression analysis program, were used to analyse the data. Some modification of the model was necessary to describe oral profiles and 40-50% of the administered PAPP appeared to be being metabolized at first pass to a non-active metabolite.
Get full access to this article
View all access options for this article.
References
1.
Bright, J.E. (1986). Prophylaxis of Cyanide Poisoning. In Clinical and Experimental Toxicology of Cyanides, eds B. Ballantyne & T. C. Marrs. Bristol: John Wright & Co., in press.
2.
Bright, J.E. & Marrs, T.C. (1982). A comparison of the methemoglobin-inducing activity of moderate oral doses of 4-dimethylaminophenol and p-aminopropiophenone. Toxicol. Lett., 13, 81-86.
3.
De Feo, F.G., Fitzgerald, T.J. & Doull, J. (1972a). Synthesis and biologic activity of para-hydroxylaminopropiophenone . Toxicol. Appl. Pharmacol., 22, 301.
4.
De Feo, F.G., Fitzgerald, T.J. & Doull, J. (1972b). Synthesis and biologic activity of p-hydroxylaminopropiophenone . J. Med. Chem., 15, 1185-1186.
5.
Downey, R.L. (1966). Radiation protection and methemoglobin-formation related to the metabolism of p-aminopropiophenone. PhD thesis, University of Indiana, pp. 59-61.
6.
Jandorf, B.J. & Bodansky, O. (1946). Therapeutic and prophylactic effect of methemoglobinemia in inhalation poisoning by hydrogen cyanide and cyanogen chloride. J. Indust. Hyg. Toxicol., 28, 125-132.
7.
Kiese, M. (1974). In Methemoglobinemia: a Comprehensive Treatise , p. 52. Cleveland: CRC Press.
8.
Marrs, T.C. & Bright, J.E. (1986). Kinetics of methaemoglobin production (1). Kinetics of methaemoglobinaemia induced by the cyanide antidotes, p-aminopropiophenone, p-hydroxyaminopropiophenone or p-dimethylaminophenol after intravenous administration . Human Toxicol., in press.
9.
Metzler, C.M., Elfring, G.L. & McEwen, A.J. (1974). A package of computer programs for pharmacokinetic modelling. Biometrics, 30, 562-570.
10.
Paulet, G., Aubertin, X., Laurens, L. & Bourrelier, J. (1963). De l'action methémoglobinisante de la paraaminopropiophénone chez l'homme, avec un complément experimentale chez le chien. Arch. Int. Pharmacodyn., 142, 35-51.
11.
Savarie, P.J., Pan, H.P., Hayes, D.J., Roberts, J.D., Dasch, G.D., Felton, R. & Schafer, E.W. (1983). Comparative acute oral toxicity of para-aminopropiophenone (PAPP) in mammals and birds. Bull. Environ. Contam. Toxicol., 30, 122-126.
12.
Scawin, J.W., Swanston, D.W. & Marrs, T.C. (1984). The acute oral and intravenous toxicity of p-aminopropiophenone (PAPP) to laboratory rodents. Toxicol. Lett., 23, 359-365.
