Plasma S-adenosylmethionine Concentrations Research Articles

Pharmacokinetic properties of S-adenosylmethionine after oral and intravenous administration of its tosylate disulfate salt: A multiple-dose, open-label, parallel-group study in healthy Chinese volunteers

Background: S-adenosylmethionine (SAMe) is an endogenous molecule that plays an important role in cellular metabolism. Despite being widely used as a dietary supplement with claimed benefits for numerous conditions, there is little information about the pharmacokinetic properties of exogenous SAMe. Objectives: One aim of this study was to characterize the pharmacokinetic properties of SAMe after administration of single and multiple doses of orally and intravenously administered SAMe tosylate disulfate (STD) in healthy male and female Chinese volunteers. Because men have higher erythrocyte levels of endogenous SAMe than do women, we also assessed the effects of sex on the disposition of SAMe. Methods: A simple and sensitive assay for SAMe based on liquid chromatography-mass spectrometry using selected-ion monitoring of analyte and acyclovir as internal standard was developed and validated. The assay was used to study the pharmacokinetic properties of SAMe. STD was administered as single and multiple doses of enteric-coated tablets and IV infusion of STD to groups of healthy native Chinese volunteers. After an overnight fast, male and female Chinese volunteers were assigned to receive STD 1000 mg for 5 days, either in enteric-coated tablet formulation or as a 250-mL IV infusion. Blood samples were collected 24 hours after the first and last dose and used for determining plasma SAMe concentrations and pharmacokinetic parameters. For the oral formulation, SAMe concentrations were corrected for concentrations of endogenous SAMe. Pharmacokinetic parameters were calculated for men and women separately and for the total group of volunteers. Adverse events were monitored using a physician during blood collection and by spontaneous reporting. Results: Twenty healthy volunteers were enrolled (oral formulation: 5 men, 5 women; mean [SD] age, 24.1 [4.7] years [range, 21–37 years]; mean [SD] weight, 59.9 [4.8] kg [range, 54–70 kg]; IV formulation: 5 men, 5 women; mean [SD] age, 22.6 [1.8] years [range, 21–27 years]; mean [SD] weight, 59.5 [5.4] kg [range, 53–67 kg]). None of the between-sex differences in SAMe pharmacokinetic properties were significant. The (mean [SD]) pharmacokinetic properties of singledose oral SAMe in men and women, respectively, were as follows: C max, 2.37 (1.58) and 2.50 (1.83) μmol/L; T max, 5.40 (1.14) and 5.20 (1.48) hours; AUC 0-24, 8.56 (5.16) and 10.3 (8.0) μmol/L/h; and t 1/2β, 6.06 (1.80) and 6.28 (2.60) hours. Corresponding values with the single-dose IV formulation were: C max, 127 (49) and 211 (94) μmol/L; T max, 1.90 (0.22) and 1.60 (0.22) hours; AUC 0-24, 329 (84) and 480 (176) μmol/L/h; and t 1/2β, 4.34 (0.57) and 3.83 (0.78) hours. The single-dose oral:IV ratios of AUC 0-24 in men and women, respectively, were 2.60% and 2.14% (degrees of fluctuation: 4.96 [1.77] and 9.49 [0.91]). The pharmacokinetic properties of multiple-dose oral and IV SAMe were not significantly different from those with single-dose administration. None of the volunteers reported any adverse events during the study. Conclusions: In this small study in healthy Chinese volunteers, there were no significant differences in the pharmacokinetic parameters of SAMe between men and women or between single- and multiple-dose administration of STD 1000 mg administered orally or intravenously. No evidence of accumulation of SAMe in plasma was found on multiple dosing. Both enteric-coated tablets and the IV infusion were well tolerated in these volunteers.

The Effects of S-Adenosylmethionine on Clinical Pathology and Redox Potential in the Red Blood Cell, Liver, and Bile of Clinically Normal Cats

S-adenosylmethionine (SAMe), an important hepatic metabolite and glutathione (GSH) donor, has been studied mechanistically in vitro, in humans with clinical liver disease, and in experimental animal models of liver disease. Collective findings encourage its therapeutic use in necroinflammatory and cholestatic liver disorders. A chronic longitudinal study (pre- and posttreatment parameters compared) was undertaken with 15 clinically healthy cats given a stable 1,4-butanedisulfonate (SS isomer) SAMe salt (enteric coated tablets providing 180 mg SAMe), dosage 48 mg/kg PO q24h, on an empty stomach for 113 days. Routine physical and clinicopathologic assessments, red blood cell (RBC) osmotic fragility, liver function and histology, hepatic concentrations of reduced GSH (RGSH) and its oxidized disulfide form (GSSG), protein, glycogen, and deoxyribonucleic acid, GSH concentrations in RBCs, total bile acids in serum and bile, oxidative membrane products (TBARS) in RBCs and liver, and plasma SAMe concentrations were evaluated. SAMe administered PO significantly increased plasma SAMe concentrations, and peak concentrations usually occurred 2–4 hours after dosing. Chronic SAMe administration did not change peak or cumulative plasma SAMe concentrations and did cause overt signs of toxicity. A positive influence on RBC and hepatic redox status (RBC TBARS reduced 21.1% [P <.002], liver GSH increased 35% [P <.002], liver RGSH:GSSG ratio increased 69% [P <.03]) and improved RBC resilience to osmotic challenge (P <.03) were observed. Results prove that this SAMe PO product is enterically available and suggest that it imparts biologic effects that might be useful for attenuating systemic or hepatic oxidant challenge

The Effects of S-Adenosylmethionine on Clinical Pathology and Redox Potential in the Red Blood Cell, Liver, and Bile of Clinically Normal Cats

S-adenosylmethionine (SAMe), an important hepatic metabolite and glutathione (GSH) donor, has been studied mechanistically in vitro, in humans with clinical liver disease, and in experimental animal models of liver disease. Collective findings encourage its therapeutic use in necroinflammatory and cholestatic liver disorders. A chronic longitudinal study (pre- and posttreatment parameters compared) was undertaken with 15 clinically healthy cats given a stable 1,4-butanedisulfonate (S'S isomer) SAMe salt (enteric coated tablets providing 180 mg SAMe), dosage 48 mg/kg PO q24h, on an empty stomach for 113 days. Routine physical and clinicopathologic assessments, red blood cell (RBC) osmotic fragility, liver function and histology, hepatic concentrations of reduced GSH (RGSH) and its oxidized disulfide form (GSSG), protein, glycogen, and deoxyribonucleic acid, GSH concentrations in RBCs, total bile acids in serum and bile, oxidative membrane products (TBARS) in RBCs and liver, and plasma SAMe concentrations were evaluated. SAMe administered PO significantly increased plasma SAMe concentrations, and peak concentrations usually occurred 2-4 hours after dosing. Chronic SAMe administration did not change peak or cumulative plasma SAMe concentrations and did not [corrected] cause overt signs of toxicity. A positive influence on RBC and hepatic redox status (RBC TBARS reduced 21.1% [P < .002], liver GSH increased 35% [P < .002], liver RGSH: GSSG ratio increased 69% [P < .03]) and improved RBC resilience to osmotic challenge (P < .03) were observed. Results prove that this SAMe PO product is enterically available and suggest that it imparts biologic effects that might be useful for attenuating systemic or hepatic oxidant challenge.