Summary
S-Adenosyl-L-methionine (AdoMet) kinetics was studied in 6 male subjects given 100 and 500 mg i. v. Drug concentrations in plasma and urine were assayed using a radioenzymatic method. Pharmacokinetic parameters were estimated according to an open two-compartment model. The apparent volumes of distribution after the 100 and 500 mg doses were 407±27 and 443±36 ml/kg (mean±SEM), terminal half-lives 81±8 and 101±7 min and body clearances 3.7±0.5 and 3.1±0.2 ml/min per kg. Urinary excretion was 34±3 and 40±2% of the administered dose. The results demonstrate that drug disposition occurs more via metabolism than via renal excretion, and it is not dependent on the administered dose. Binding of AdoMet to serum proteins is negligible.
References
Curcio M, Catto E, Stramentinoli G, Algeri S (1978) Effect of S-adenosyl-L-methionine on serotonin metabolism in rat brain. Prog Neuro-Psychopharmacol 2: 65–71
Algeri S, Catto E, Curcio M, Ponzio F, Stramentinoli G (1979) Changes in rat brain noradrenaline and serotonin metabolism after administration of S-adenosylmethionine. In: Zappia V, Usdin E, Salvatore F (eds) Biochemical and pharmacological roles of adenosylmethionine and the central nervous system. Pergamon Press, Oxford
Stramentinoli G, Catto E, Algeri S (1980) Decrease of noradrenaline O-methylation in rat brain induced by L-dopa. Reversal effect of S-adenosyl-L-methionine. J Pharm Pharmacol 32: 430–431
Cimino M, Curatola G, Pezzoli C, Stramentinoli G, Vantini G, Algeri S (1983) Age-related modification of dopaminergic and β-adrenergic receptor system: restoration of normal activity by modifying membrane fluidity with S-adenosylmethionine. In: Agnoli A, Crepaldi G, Spano PF, Trabucchi M (eds) Aging brain and ergot alkaloids. Raven Press, New York
Stramentinoli G, Pezzoli C, Galli-Kienle M (1979) Protective role of S-adenosyl-L-methionine against acetaminophen-induced mortality and hepatotoxicity in mice. Biochem Pharmacol 28: 3567–3571
Stramentinoli G, Gualano M, Di Padova C (1977) Effect of S-adenosyl-L-methionine on ethynylestradiol-induced impairment of bile flow in female rats. Experientia 33: 1361–1362
Stramentinoli G, Gualano M, Rovagnati P, Di Padova C (1979) Influence of S-adenosyl-L-methionine on irreversible binding of ethynylestradiol to rat liver microsomes, and its implication in bile secretion. Biochem Pharmacol 28: 981–984
Stramentinoli G, Di Padova C, Gualano M, Rovagnati P, Galli-Kienle M (1981) Ethynylestradiol-induced impairment of bile secretion in the rat: protective effects of S-adenosyl-L-methionine and its implication in estrogen metabolism. Gastroenterology 80: 154–158
Di Padova C, Tritapepe R, Cammareri G, Humpel M, Stramentinoli G (1982) S-adenosyl-L-methionine antagonizes ethynyl estradiol-induced bile cholesterol supersaturation in humans without modifying the estrogen plasma kinetics. Gastroenterology 82: 223–227
Boelsterli UA, Rakhit G, Balazs T (1983) Modulation by S-adenosyl-L-methionine of Hepatic Na+, K+-ATPase, membrane fluidity, and bile flow in rats with ethinyl estradiol-induced cholestasis. Hepatology 3: 12–17
Schreiber AJ, Warren G, Sutherland E, Simon FR (1983) Enhancement of Taurocholate secretory maximum: S-adenosylmethionine (SAM)-induced cytoprotection. Clin Res 31: 86A
Schreiber AJ, Sutherland E, Simon FR (1982) Prevention of ethinyl estradiol (EE) cholestasis by S-adenosyl-methionine (SAMe): possible role of phosphatidylcholine (PC). Hepatology 2: 697
Agnoli A, Andreoli V, Casacchia M, Cerbo R (1976) Effect of S-adenosyl-L-methionine (SAMe) upon depressive symptoms. J Psychiatr Res 13: 43–54
Miccoli L, Porro V, Bertolino A (1978) Comparison between the antidepressant activity of S-adenosyl-methionine (SAMe) and that of some tricyclic drugs. Acta Neurol 33: 243–255
Carney MWP, Martin R, Bottiglieri T, Reynolds EH, Nissenbaum H, Toone BK (1983) Switch mechanism in affective illness and S-adenosylmethionine. Lancet 1: 820–821
Lipinski JF, Cohen BM, Frankenburg F, Tohen M, Waternaux C, Altesman R, Jones B, Harris P (1984) S-adenosyl-L-methionine in the treatment of depression. Results of an open trial. Am J Psychiatr 141: 448–450
Frezza M, Pozzato G, Chiesa L, Stramentinoli G, Di Padova C (1984) Reversal of intrahepatic cholestasis of pregnancy in women after high dose S-adenosyl-L-methionine (SAMe) administration. Hepatology 4: 274–278
Di Padova C, Tritapepe R, Stramentinoli G (1984) S-adenosyl-L-methionine prevents cholesterol supersaturation of gall-bladder bile in women during oral contraceptive use. Ital J Gastroenterol (in press)
Placidi GF, Stramentinoli G, Cassano GB (1977) Distribution of S-adenosyl-L-(methyl-14C) methionine in animals. Arzneimittelforsch (Drug Res) 27: 1680–1684
Stramentinoli G, Catto E (1976) Pharmacokinetic studies of S-adenosyl-L-methionine (SAMe) in several animal species. Pharmacol Res Commun 8: 211–218
Giulidori P, Stramentinoli G (1984) A radioenzymatic method for S-Adenosyl-L-methionine determination in biological fluids. Anal Biochem 137: 217–220
Gibaldi M, Perrier D (1975) Pharmacokinetics. Marcel Dekker, New York
Sacchi-Landriani G, Guardabasso V, Rocchetti M (1983) NLFIT: A microcomputer program fro non-linear fitting. Comput Progr Biomed 16: 35–42
Giulidori P, Galli-Kienle M, Catto E, Stramentinoli G (1984) Transmethylation, transsulfuration, and aminopropylation reactions of S-Adenosyl-L-Methionine in vivo. J Biol Chem 259: 4205–4211
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Giulidori, P., Cortellaro, M., Moreo, G. et al. Pharmacokinetics of S-adenosyl-L-methionine in healthy volunteers. Eur J Clin Pharmacol 27, 119–121 (1984). https://doi.org/10.1007/BF02395218
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DOI: https://doi.org/10.1007/BF02395218