EFFECTS OF YOHIMBINE ON AUTONOMIC MEASURES ARE DETERMINED BY INDIVIDUAL-VALUES FOR AREA UNDER THE CONCENTRATION-TIME CURVE

A study was conducted to examine tolerability and pharmacodynamics of single doses of yohimbine in healthy Volunteers using measures of mood , heart rate, blood pressure, and serum catecholamine levels, Particip ants were given single oral doses of yohimbine hydrochloride as high a s 21.6 mg. Plasma concentrations of yohimbine, epinephrine, norepineph rine, and MHPG (3-methoxy-4-hydroxyphenylethylene-glycol) were quantif ied by means of high-performance liquid chromatography with electroche mical detection. Mood was assessed by visual analogue scale (VAS), the Profile of Mood States, and the Spielberger State Anxiety Index, Yohi mbine was well tolerated and rapidly absorbed and eliminated. Dose-rel ated increases in area under the concentration-time curve (AUC) were o bserved. Administration of yohimbine in the presence of a high fat mea l diminished both the rate and extent of drug absorption. Significant intersubject variability in the pharmacokinetic parameters of yohimbin e was observed, with some individuals exhibiting greatly increased ora l bioavailability of yohimbine, Increases in blood pressure, respirato ry rate, plasma catecholamine levels, and total VAS score were observe d in participants with elevated AUC values. The AUC of yohimbine had t he largest effect on total VAS score. The results indicate that higher doses of yohimbine are both well tolerated and produce dose-related i ncreases in AUG, which are associated with more pronounced autonomic e ffects. Increases in respiratory rate and plasma MHPG appear to be the most reliable pharmacodynamic measures for single oral doses of yohim bine. Individual differences in the pharmacokinetics of yohimbine are important in determining pharmacodynamic effects and should be conside red in evaluations of its clinical effectiveness.