A comparison of tissue gold levels in guinea-pigs after treatment with Myocrisin injected intramuscularly and triethylphosphine gold chloride and Myocrisin administered orally

Agents and Actions - Tập 8 - Trang 546-550 - 1978
H. Kamel1, D. H. Brown1, J. M. Ottaway1, W. E. Smith1, J. Cottney2, A. J. Lewis2
1Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow
2Scientific Development Group, Organon Laboratories Ltd., Newhouse

Tóm tắt

A comparative study of tissue gold levels produced in guinea-pigs after the oral administration of either triethyl-phosphine gold chloride or Myocrisin (sodium aurothiomalate) or after the injection of Myocrisin intramuscularly is reported. Gold concentrations were determined 5, 24 and 168 hours after administration in stomach, small intestine, large intestine, kidney, liver and spleen and 5 and 24 hours after administration in skin, adrenals, heart, lung and brain. In gastrointestinal tissues, tissue gold concentrations were highest with triethylphosphine gold chloride. The stomach gold level 5 hours after oral administration of triethyl-phosphine gold chloride is particularly high and, taken in conjunction with the other gastrointestinal gold levels measured, suggests that a stomach rather than an intestinal absorption mechanism may predominate. A more extensive time-course study on kidney and liver is reported and the possible relationship between tissue concentration and toxicity is discussed.

Tài liệu tham khảo

D.T. Walz, M.J. DiMartino andB.M. Sutton,Design and Evaluation of Gold Compounds as Anti-Inflammatory Agents in Anti-Inflammatory Agents, vol. 1 (Eds. R.A. Sherrer and M.A. Whitehouse; Academic Press, New York, 1974). D.T. Walz, M.J. DiMartino, L.W. Chakrin, B.M. Sutton andA. Misher,Anti-Arthritic Properties and Unique Pharmacological Profile of a Potential Chrysotherapeutic Agent, S.K. and F. D39162, J. Pharmac. exp. Ther.197, 142–152 (1976). E.R. McGusty andB.M. Sutton.Anti-Arthritic Compositions Comprising Phosphine and Phosphite Gold Halide Complexes and Methods of Producing Anti-Arthritic Activity, U.S. Patent No. 3,676,554 (1972). A.E. Finkelstein, D.T. Walz, V. Batista, M. Mizraji, F. Roisman andA. Misher,Auranofin. New Oral Gold Compound for Treatment of Rheumatoid Arthritis, Ann. Rheum. Dis.35, 251–257 (1976). H. Kamel, D.H. Brown, J.M. Ottaway, W.E. Smith, J. Cottney andA.J. Lewis,Serum Levels of Gold in Guinea-Pigs after Oral Administration of Different Compounds Compared to Myocrisin Injected Intramuscularly. Arthritis Rheum. (Accepted for publication). H. Kamel, D.H. Brown, J.M. Ottway andW.E. Smith,Determination of Gold in Blood Fractions by Atomic Absorption Spectrometry Using Carbon Rod and Carbon Furnace Atomisation, Analyst101, 790–797 (1976). H. Kamel, D.H. Brown, J.M. Ottaway andW.E. Smith,Determination of Gold in Separated Blood Protein Fraction by Carbon Furnace Atomic Absorption Spectrometry, Analyst102, 645–657 (1977). H. Kamel, D.H. Brown, J.M. Ottaway andW.E. Smith,The Determination of Gold in Tissue by Carbon Furnace Atomic Absorption Spectrometry, Talanta24, 309–313 (1977). W.D. Block, O.H. Buchanan andR.H. Freyberg,Metabolism, Toxicity and Manner of Action of Gold Compounds Used in the Treatment of Arthritis, J. Pharmac. exp. Ther.82, 391–398 (1944). M.R. Jeffrey, H.F. Freundlich andD.M. Bailey,Distribution and Excretion of Radiogold in Animals, Ann. Rheum. Dis.17, 52–60 (1958). E.G. McQueen andP.W. Dykes,Transport of Gold in the Body, Ann. Rheum. Dis.28, 437–442 (1969). H.A. Swartz, J.E. Christian andF.N. Andrews,Distribution of Sulphur-35 and Gold-198 Labelled Thioglucose in Mice, Amer. J. Physiol.199, 67–70 (1960). J.J. Bertrand, H. Waine andC.A. Tobias,Distribution of Gold in Animal Body in Relation to Arthritis, J. Lab. Clin. Med.33, 1133–1138 (1948). N.L. Gotlieb, P.M. Smith andE.M. Smith,Tissue Gold Concentrations in Rheumatoid Arthritics Receiving Chrysotherapy, Arthritis Rheum.15, 16–22 (1972). H. Kamel, D.H. Brown, J.M. Ottaway, W.E. Smith, W.H.R. Auld andM.E. Cunningham,Gold Levels in Kidney, Liver and Spleen, Arthritis Rheum.19, 1368 (1976). D.H. Brown, G. McKinlay andW.E. Smith,The Electronic and Circular Dichroism Spectra of Gold (I) Complexes with Sulphur and Phosphorus-Containing Ligands, J. Chem. Soc. (Dalton Transactions) 1874–1879 (1977). D.H. Brown, G. McKinlay andW.E. Smith,The Reactions of l-Cysteine and d -Penicillamine with Gold, J. Chem. Soc. (Dalton Transactions) (in press). R.H. Freyberg,Gold Therapy for Rheumatoid Arthritis in Arthritis and Allied Conditions (Ed. J.L. Hollander; H. Kimpton, London, 1972).