Ex vivo/In vitro Interaction between ASA, Clopidogrel and GPIIb/IIIa-Inhibitors

1999 ◽  
Vol 19 (03) ◽  
pp. 112-114
Author(s):  
C. M. Kirchmaier ◽  
Dagmar Westrup ◽  
J. Graff ◽  
R. Mahnel ◽  
H. K. Breddin ◽  
...  

SummaryWe report on an in vivo interaction study between aspirin (ASA) and Clopidogrel in healthy male volunteers and on an in-vitro interaction of abciximab and the peptidomimetic GPIIb/IIIa-inhibitor SR121566A with blood from subjects of the in vivo-study. Ten healthy male volunteers were randomly assigned to two groups (N = 5). Group 1 started with ASA and group 2 with Clopidogrel. From day 4 to 8 subjects of both groups received combined treatment with ASA and Clopidogrel. Blood from volunteers was spiked with abciximab or SR121566A. Inhibitory effects of ASA and Clopidogrel on collagen- or ADP-induced platelet aggregation were not enhanced by the combination of both drugs. TRAP-induced fibrinogen binding was reduced under ASA to 69% (n.s.), and to 63% under Clopidogrel or Clopidogrel + ASA. CD62-expression was reduced to 66% by Clopidogrel (p <0.01 ), whereas ASA had no effect. A further significant reduction to 41 % (difference to clopidogrel/ASA alone p <0.01), was seen under combined treatment (day 8). ASA and Clopidogrel increased the effects of the GPIIb/IIIa-inhibitors on collagen (2 pg/ml)- and ADP (5 pM)-induced aggregation. Under treatment with ASA and Clopidogrel inhibitory effects of GPIIb/IIIa-inhibitors on fibrinogen binding were additive to changes seen with ASA/clopidogrel alone. No additional effect on CD62 was seen with either GPIIb/IIIa-inhibitor.

1996 ◽  
Vol 135 (2) ◽  
pp. 193-197 ◽  
Author(s):  
Markus Banger ◽  
Christoph Hiemke ◽  
Margitta Haupt ◽  
Rudolf Knuppen

Banger M, Hiemke C, Haupt M, Knuppen R. Excretion of 2- and 3-monomethyl ethers of 2-hydroxyestrogens in healthy male volunteers. Eur J Endocrinol 1996;135:193–7. ISSN 0804–4643 The formation of catecholestrogens by 2-and 4-hydroxylation of monophenolic estrogens represents a major route of estrogen metabolism. In vitro and in vivo studies on catecholestrogens have shown that 2-hydroxylated catecholestrogens are primarily inactivated by O-methylation, while O-methylation of 4-hydroxylated estrogen is of minor importance. In the present study the in vivo production of isomeric 2- and 3-monomethyl ethers of 2-hydroxyestrogens was measured in 12 healthy omnivorous male volunteers aged 51 ± 4 years. The sum of estrone and 17β-estradiol, 2-hydroxyestrogens (sum of 2-hydroxyestrone and 2-hydroxyestradiol), 4-hydroxyestrogens (sum of 4-hydroxyestrone and 4-hydroxyestradiol) and the sum of the isomeric monomethyl ethers of 2-hydroxyestrone and 2-hydroxyestradiol were measured in 24-h urinary samples. The determinations included hydrolysis of steroid conjugates, separation by chromatographic steps and final quantification by radioimmunoassay. The specificity of the antibodies enabled differentiation between the isomeric monomethyl ethers. The mean urinary excretion rates were 8.8 ± 2.9 μg/24 h for estrone plus estradiol, 5.2 ± 2.4 μg/24 h for the 2-hydroxyestrogens and 1.3 ± 0.5 μg/24 h for the 4-hydroxyestrogens. The 2- and 3-monomethyl ethers of the 2-hydroxyestrogens were found in all individuals, with excretion rates of 5.8 ± 2.6 μg/24 h for 2-methoxyestrogens and 3.6 ± 1.1 μg/24 h for 2-hydroxyestrogen-3-methyl ethers. The findings indicated that 2-hydroxyestradiol is metabolized in vivo by 2-O-methylation and, to a lesser extent, by 3-O-methylation. Markus Banger, Department of Psychiatry, University of Essen, Virchowstr. 174, 45147 Essen, Germany


2020 ◽  
Vol 48 (10) ◽  
pp. 873-885
Author(s):  
Ulrike Glaenzel ◽  
Yi Jin ◽  
Regine Hansen ◽  
Kirsten Schroer ◽  
Gholamreza Rahmanzadeh ◽  
...  

Author(s):  
M Usman ◽  
M Ahmad ◽  
AU Madni ◽  
NAW Asghar ◽  
M Akhtar ◽  
...  

1984 ◽  
Vol 106 (2) ◽  
pp. 193-198 ◽  
Author(s):  
Hitoshi Ikeda ◽  
Shoo Cheng Chiu ◽  
Nobuaki Kuzuya ◽  
Hidemasa Uchimura ◽  
Shigenobu Nagataki

Abstract. The present study was undertaken to examine the effects of prolonged in vivo treatment with T3 and long acting thyroid stimulator (LATS) on in vitro responsiveness of mouse thyroid cyclic AMP to thyrotrophin (TSH) and LATS-immunoglobulin G (IgG). In control mice, thyroid cAMP concentrations after incubation with normal-IgG (10 mg/ml) for 2 h. TSH (10 mU/ml) for 10 min and LATS-IgG (10 mg/ml) for 2 h were 1.25 ± 0.11 (mean ± se) (n = 5), 15.87 ± 3.47 (n = 6) and 2.17 ± 0.25 pmoles/mg wet weight (n = 6), respectively. In mice given T3 (5 μg/ml in drinking water for 5 days, thyroid cAMP concentrations after an incubation with TSH were reduced by 50%, as compared to those of the control mice. They were also decreased in mice injected ip with 5 mg of LATS-IgG (1000%/5 mg in the McKenzie bioassay) daily for 5 days. Combined treatment with T3 and LATS decreased the cAMP response to TSH only to the same extent as did T3 alone, indicating that the inhibitory effects of T3 and LATS were not additive. Similar findings were observed with the thyroid cAMP response to LATS-IgG in vitro; either T3 or LATS treatment in vivo decreased cAMP response to LATS-IgG in vitro, but combined treatment with T3 and LATS did not cause further inhibition as compared with T3 or LATS treatment alone. These results indicate, 1) that prolonged in vivo T3 treatment inhibits the in vitro thyroid cAMP response not only to TSH but also to LATS-IgG, 2) that prolonged in vivo LATS treatment also suppresses the thyroid cAMP response both to TSH and LATS-IgG and 3) that the inhibitory effects of LATS may not be due to the effects of LATS per se but to increases in circulating thyroid hormone levels induced by prolonged LATS treatment.


1997 ◽  
Vol 41 (6) ◽  
pp. 1319-1321 ◽  
Author(s):  
P E Rolan ◽  
A J Mercer ◽  
E Tate ◽  
I Benjamin ◽  
J Posner

Atovaquone is an antiprotozoal compound with good in vitro stability against metabolic inactivation. Previous human studies which did not involve radiolabelling had not accounted for a substantial proportion of the dose. The possible metabolism of atovaquone in men was examined in a radiolabelling study involving four healthy male volunteers. Radioactivity was eliminated almost exclusively via the feces. All radioactivity in plasma, urine, and feces was accounted for by atovaquone, with no evidence of metabolites. Radiolabelled atovaquone was administered to a patient with an indwelling biliary tube after surgery. Biliary radioactivity was approximately 10- to 40-fold higher than that in plasma and was accounted for by atovaquone. Atovaquone is not significantly metabolized in humans but is excreted into bile against a high concentration gradient.


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