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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Disposition of a new orally active dopamine prodrug, N-(N-acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl) dopamine (TA-870) in humans.

Dopamine (DA) levels in human plasma after oral administration of TA-870 and iv infusion of DA were measured by HPLC. The metabolites of TA-870 or DA in plasma and urine were also determined. The maximal concentrations (Cmax) of free DA in plasma after oral administration of 750 and 1500 mg of TA-870 to humans were 63 and 127 ng/ml, respectively, being higher than the concentrations of 8 and 31 ng/ml following the infusion of 1 and 3 micrograms/kg/min, the clinical doses of DA. These results demonstrated the clinical usefulness of TA-870. The plasma level of free deethoxycarbonylated TA-870 (DEC-TA-870) after oral administration of TA-870 was higher than that of DA. After oral administration of TA-870, the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC) in plasma was higher than that after DA infusion, but the concentration of homovanillic acid (HVA) was about the same as that after DA infusion. The level of the total urinary metabolites (free and conjugated) after oral administration of TA-870 decreased as follows: DA greater than HVA greater than DOPAC greater than DEC-TA-870. The conjugated/free ratios of urinary metabolites after TA-870 dosing were 40-66 for DA, 0.5 for HVA, 0.6-0.9 for DOPAC, and 5.0-6.2 for DEC-TA-870. The composition of urinary metabolites after oral dosing of TA-870 was almost the same as that the DA metabolites. These results show that TA-870 is rapidly converted to DA in the human body.[1]

References

  1. Disposition of a new orally active dopamine prodrug, N-(N-acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl) dopamine (TA-870) in humans. Yoshikawa, M., Endo, H., Komatsu, K., Fujihara, M., Takaiti, O., Kagoshima, T., Umehara, M., Ishikawa, H. Drug Metab. Dispos. (1990) [Pubmed]
 
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