Summary
o,p'-DDD is an inhibitor of adrenal steroid synthesis currently used for therapy of Cushing's syndrome. Conflicting data have been published on the relationship between the plasma level of the drug and its clinical and biological effects. The levels of o,p'-DDD and o,p'-DDE in various tissues obtained from treated patients have been measured and are compared with data on in vitro steroidogenesis in adrenal tissues from the same patients. o,p'-DDD was found in all samples and o,p'-DDE in half of them, both levels being high when the tissue lipid concentration was high. There was considerable variability in lipid content from one tissue to another and within a tissue from one sample to another; only the drug to lipid ratio seems able to provide a reproducible index of drug entry into a tissue. No relationship was found between the tissue concentration of the drug and the total dose administered or inhibition of the steroid biosynthetic step studied.
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References
Hutter AM, Kayhoe DE (1966) Adrenal cortical carcinoma. Results of treatment with o,p'-DDD in 138 patients. Am J Med 41: 581–592
Hellman L, Weitzman ED, Roffwarg H, Fukushima DK, Yoshida K, Zumoff B, Gallagher TF (1970) Effect of o,p'-DDD on cortisol secretory pattern in Cushing's syndrome. J Clin Endocrinol Metab 31: 227–230
Luton JP, Mahoudeau JA, Bouchard P, Thieblot P, Hautecouverture M, Simon D, Laudat MH, Touitou Y, Bricaire H (1979) Treatment of Cushing's disease by o,p'-DDD. Survey of 62 cases. N Engl J Med 300: 459–464
Touitou Y, Bogdan A, Legrand JC, Desgrez P (1977) Métabolisme de l'o,p'-DDD (mitotane) chez l'homme et l'animal. Ann Endocrinol 38: 13–25
Orth DN, Liddle GW (1971) Results of treatment in 108 patients with Cushing's syndrome. N Engl J Med 285: 243–247
Touitou Y, Bogdan A, Luton JP (1978) Changes in corticosteroid synthesis of the human adrenal cortex in vitro, induced by treatment with o,p'-DDD for Cushing's syndrome: Evidence for the sites of action of the drug. J Steroid Biochem 9: 1217–1224
Touitou Y, Bogdan A (1978) Influences of o,p'-DDD, o,p'-DDE and solubilization procedures on the in vitro biosynthesis of 18-hydroxycorticosterone and aldosterone by sheep adrenals. Int J Biochem 9: 691–695
Touitou Y, Bogdan A, Auzéby A, Dommergues JP (1979) Glucocorticoid and mineralocorticoid pathways in two adrenocortical carcinomas: comparison of the effects of o,p'-DDD, aminoglutethimide and 2-p-aminophenyl-2-phenylethylamine in vitro. J Endocrinol 82: 87–94
Moy RH (1961) Studies of the pharmacology of o,p'-DDD in man. J Lab Clin Med 58: 296–304
Moolenaar AJ, Van Slooten H, Van Seters AP, Smeenk D (1981) Blood levels of o,p'-DDD following administration in various vehicles after a single dose and during long term treatment. Cancer Chemother Pharmacol 7: 51–54
Van Slooten H, Van Seters AP, Smeenk D, Moolenaar AJ (1982) o,p'-DDD (mitotane) levels in plasma and tissues during chemotherapy and at autopsy. Cancer Chemother Pharmacol 9: 85–88
Van Slooten H, Moolenaar AJ, Van Seters AP, Smeenk D (1982) The treatment of adrenocortical carcinoma with o,p'-DDD: Prognostic implications of serum level monitoring. Eur J Cancer Clin Oncol 20: 47–53
Moolenaar AJ, Niewint JWM, Oei IT (1977) Estimations of o,p'-DDD in plasma by gas liquid chromatography. Clin Chim Acta 76: 213–218
Harding BW, Nelson DH (1966) Electron carriers of the bovine adrenal cortical respiratory chain and hydroxylating pathways. J Biol Chem 241: 2212–2219
Lowry O, Rosebrough MJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin-phenol reagent. J Biol Chem 193: 265
Cueto C, Brown JHU (1958) Biological studies on an adrenocorticolytic agent and the isolation of the active components. Endocrinology 62: 334–339
Touitou Y, Bogdan A, Auzéby A (1983) Experimental evidence for biosynthesis of steroids in metastatic tissue originating from a primitive adrenocortical carcinoma. Int J Biochem 15: 571–573
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Touitou, Y., Moolenaar, A.J., Bogdan, A. et al. o, P'-DDD (mitotane) treatment for Cushing's syndrome: Adrenal drug concentration and inhibition in vitro of steroid synthesis. Eur J Clin Pharmacol 29, 483–487 (1985). https://doi.org/10.1007/BF00613466
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DOI: https://doi.org/10.1007/BF00613466