Pharmacokinetics and effects of oral hydroxy-3(S)-dihydroquinidine (3-OH-HQ) on heart rate (HR), blood pressure (BP), and ECG intervals were studied in 12 healthy volunteers. Three oral single doses of 3-OH-HQ (225, 450, and 900 mg) and placebo were randomly administered to each subject at one week intervals. Pharmacokinetics of 3-OH-HQ was linear in the range of administered doses, with rapid absorption (tmax 0.5-2.5 h) and distribution (t1/2 alpha 0.8-1.2 h) phases. Elimination half-lives did not significantly change with the three doses (15 +/- 4.3, 13.7 +/- 3.9, and 13 +/- 2.2 h). Unchanged 3-OH-HQ was partially eliminated by urine (mean renal clearance 0.24 +/- 0.02 L h-1 kg-1). 3-OH-HQ significantly increased HR after the three doses as compared to placebo. PR interval was not significantly modified but QRS duration significantly increased from 91 +/- 7 to 108 +/- 11 ms (p less than 0.001) 2 h after the 900 mg dose. QTc interval was significantly prolonged from 0.5 to 8 h after the highest dose (14.4 +/- 8.7% 1 h after dosing). Heart rate QRS, and QTc variations were significantly correlated to 3-OH-HQ plasma levels.