Metabolic Fate of Dopamine Prodrug TA-870. (1): Absorption, Distribution and Excretion in Rats and Dogs.

Yoshikawa, Masayoshi; Endô, Hiroshi; Hoshino, Kumiko; Takaiti, Osasi

doi:10.2133/dmpk.6.243

Cited by 2 publications

(7 citation statements)

References 6 publications

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“…spectively (38). The C,, of free DA after oral administration of docarpamine was 150 ng/ml in the rat (30 mgkg) and 234 ng/ml in the dog (33.5 mg/kg).…”

Section: Absorption Distribution Metabolism and Excretion In Animalsmentioning

confidence: 90%

“…Urinary and fecal excretion rates within 72 h in dogs were 56.4 and 37.4%, respectively. Biliary excretion of radioactivity within 24 h after oral administration to male rats was 19.8% of the dose given (38).…”

Section: Absorption Distribution Metabolism and Excretion In Animalsmentioning

confidence: 93%

“…The in situ absorption of [3H]docarpamine from the digestive tract (600 pg/loop) was approximately 88% within 6 h. The absorption rate, calculated from the area under the curve (AUC) of plasma radioactivity and the urinary excretion, after oral and intravenous administration of ['4C]docarpamine (30 mg/kg) to male rats was 84.3 and 89.4%, re-spectively (38). The C,, of free DA after oral administration of docarpamine was 150 ng/ml in the rat (30 mgkg) and 234 ng/ml in the dog (33.5 mg/kg).…”

Section: Absorption Distribution Metabolism and Excretion In Animalsmentioning

confidence: 97%

“…The tissue distribution of radioactivity after oral administration of ['4C]docarpamine (30 mg/kg) was highest in the digestive tract and liver, followed, in decreasing order, by the kidney > plasma > lung > skin :> pancreas > myocardium > thymus > testis > skeletal muscle > brain (38). In both fetuses and neonates, the radioactivity transferred from maternal rats was less than 0.05% of the dose given (1).…”

Section: Absorption Distribution Metabolism and Excretion In Animalsmentioning

confidence: 99%

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An Orally Effective Peripheral Dopamine Prodrug: Docarpamine (TA‐870)

Nishiyama

Yoshikawa

Yamaguchi

1992

Cardiovascular Drug Reviews

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Intravenous infusion of dopamine (DA) has been widely used in patients with acute heart failure, shock, and acute renal failure (4-7,18,19). However, since DA is rapidly inactivated by sulfotransferase, monoamine oxidase (MAO), and catechol-0-methyltransferase (COMT) in the intestinal wall and liver, plasma free DA levels scarcely rise to therapeutically effective concentrations when this drug is administered orally (20,22,35,36).Docarpamine is a derivative of DA that was designed as an orally active prodrug (36). It effectively elevates the plasma free DA level by reducing first-pass metabolism when administered by the enteric route (43). Oral docarpamine shows renal vasodilatory and natriuretic effects by activating renal DA, receptors, and a positive inotropic effect by activating cardiac PI-receptors via free DA (26,28-30,36). Docarpamine and its metabolites do not cross the blood-brain barrier, and show no effect on the central nervous system (CNS) even at high doses (3). It has a weaker emetic effect than levodopa (25). Clinical trials show that docarpamine can be used as a practical alternative to DA infusion (8,15,17,21,37). Docarpamine is an orally effective peripheral DA prodrug capable of improving renal and cardiac function by oral administration. CHEMISTRYDocarpamine was designed to protect the catechol and amino moieties of DA with ethoxycarbonyl and acetylmethionyl groups, respectively. The chemical name of docarpamine is N-(N-acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)dopamine (Fig. 1). Its molecular weight is 470.54, the empiric formula is C,,H&O,S, and its melting point is 105-108°C. Docarpamine is available as a white crystalline powder. It is slightly soluble in water, and readily soluble in ethanol.

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“…spectively (38). The C,, of free DA after oral administration of docarpamine was 150 ng/ml in the rat (30 mgkg) and 234 ng/ml in the dog (33.5 mg/kg).…”

Section: Absorption Distribution Metabolism and Excretion In Animalsmentioning

confidence: 90%

Section: Absorption Distribution Metabolism and Excretion In Animalsmentioning

confidence: 93%

Section: Absorption Distribution Metabolism and Excretion In Animalsmentioning

confidence: 97%

Section: Absorption Distribution Metabolism and Excretion In Animalsmentioning

confidence: 99%

See 2 more Smart Citations

An Orally Effective Peripheral Dopamine Prodrug: Docarpamine (TA‐870)

Nishiyama

Yoshikawa

Yamaguchi

1992

Cardiovascular Drug Reviews

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“…HPLC has also been employed in determining trimebutine maleate and its metabolites in rat plasma (Miura et al, 1998). Radiometric analysis with either 14 C or 3 H labeled trimebutine maleate has been described for studying its distribution in tissue of rats, mice and dogs with different distribution patterns of radioactivity between the labeled compounds due to the metabolism of the drug (Yoshikawa et al, 1982). In our previous report a high-performance capillary electrophoresis method was described for assaying the content of trimebutine maleate in capsules (Yu and Li, 2000).…”

Section: Introductionmentioning

confidence: 99%

Determination of trimebutine maleate in rat plasma and tissues by using capillary zone electrophoresis

2001

Biomedical Chromatography

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A simple and rapid capillary zone electrophoresis method was developed for the determination of trimebutine maleate in rat plasma and tissues. Rat plasma and tissue homogenates were mixed with acetonitrile containing internal standard, ephedrine hydrochloride, and then centrifuged. The supernatant was dried under a stream of nitrogen, and the residue was reconstituted in methanol-water (1:1). The electrophoresis was performed in uncoated capillary with 30 mmol/L phosphate buffer of pH 6.0 as the separation electrolyte. The applied voltage was 10 kV and the UV detection was set at 214 nm. The peak height ratio vs concentration in plasma or homogenates was linear over the range of 5-500 ng/mL and the limit of quantitation was 5 ng/mL. The intra- and inter-day precision was RSD < 14% and <15%. The accuracy was relative error (RE) within +/- 14%. This method was applied to studying the pharmacokinetics and tissue distribution after a single dose of trimebutine maleate was administrated to the rats. The T(max), AUC, C(max) and t(1/2) were 30 min, 7.8 x 10(2) (ng/mL) min, 39 ng/mL and 1.7 x 10(2) min. The drug distribution was found in a decreasing order of liver, kidney, spleen, lung and heart.

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Metabolic Fate of Dopamine Prodrug TA-870. (1): Absorption, Distribution and Excretion in Rats and Dogs.

Cited by 2 publications

References 6 publications

An Orally Effective Peripheral Dopamine Prodrug: Docarpamine (TA‐870)

An Orally Effective Peripheral Dopamine Prodrug: Docarpamine (TA‐870)

Determination of trimebutine maleate in rat plasma and tissues by using capillary zone electrophoresis

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