Bioavailability and pharmacokinetics of oral dopamine in dogs.
The bioavailability and pharmacokinetics of oral dopamine (DA) were studied in dogs. Plasma concentrations of DA and its main metabolites, such as dopamine-3-O-sulfate (DA-SO4) and 3,4-dihydroxyphenyl acetic acid (DOPAC) were determined after intravenous or oral administration of DA using high-performance liquid chromatography with electrochemical detector (HPLC-ECD). Following the intravenous administration, plasma DA-SO4 and DOPAC concentrations were lower than the plasma DA concentration. On the other hand, following the oral administration, plasma DA-SO4 and DOPAC concentrations were much higher than the plasma DA concentration. The absolute bioavailability of DA after oral administration was calculated to be approximately 3%. Intraduodenal and mesenteric venous administration of DA revealed that DA-SO4 was mainly produced in the intestine and DOPAC was produced in the intestine and liver. On the basis of these observations, the bioavailability and pharmacokinetics of oral DA are discussed in connection with the metabolic inactivation due to first-pass metabolism.
Murata
K
K
Products Formulation Research Laboratory, Tanabe Seiyaku Company, Ltd., Osaka, Japan.
Noda
K
K
Kohno
K
K
Samejima
M
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D004298:Dopamine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D004386:Duodenum; D007275:Injections, Intravenous; D007441:Intubation, Gastrointestinal
D015102:3,4-Dihydroxyphenylacetic Acid; C022807:dopamine 4-O-sulfate; D004298:Dopamine