Ibopamine kinetics after a single oral dose in healthy volunteers.

In order to describe kinetics after single administration and to test dose independence in the therapeutic dose range, ibopamine (SB-7505), the 3,4-diisobutyrylester of N-methyldopamine (epinine), was given orally to six healthy volunteers at multiple dose levels in a cross-over fashion. Doses employed were 50, 100 and 200 mg with a wash-out period of at least three days between doses. Plasma levels were studied after the 100 mg dose, and urinary recoveries of the major metabolites were measured after each dose. After oral intake of ibopamine, both conjugated and free epinine were detectable in plasma at the earliest sampling times (i.e. 5-10 min), with a hybrid absorption half-life of 0.25 h. Peak plasma concentration mean values of total and free epinine were 33 mumol/l and 35 nmol/l, respectively, and mean time to plasma peak concentration was 1.5 and 0.71 h, respectively. 24-h urinary recovery of conjugated epinine, homovanillic acid and dihydroxyphenylacetic acid accounted for about two thirds of the dose, without dose-dependent mechanisms affecting total elimination. Presystemic sulfate conjugation as a potentially saturable metabolic step at higher dose levels is discussed, although evidence was not found of its saturation in the studied dose range.