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Grasing, K; Sturgill, M G; Rosen, R C; Trout, J R; Thomas, T J; Kulkarni, G D; Maines, P; Seibold, J R
Journal of clinical pharmacology, September 1996, Letnik: 36, Številka: 9Journal Article
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. Participants were given single oral doses of yohimbine hydrochloride as high as 21.6 mg. Plasma concentrations of yohimbine, epinephrine, norepinephrine, and MHPG (3-methoxy-4-hydroxyphenylethylene-glycol) were quantified by means of high-performance liquid chromatography with electrochemical detection. Mood was assessed by visual analogue scale (VAS), the Profile of Mood States, and the Spielberger State Anxiety Index. Yohimbine was well tolerated and rapidly absorbed and eliminated. Dose-related increases in area under the concentration-time curve (AUC) were observed. Administration of yohimbine in the presence of a high fat meal diminished both the rate and extent of drug absorption. Significant intersubject variability in the pharmacokinetic parameters of yohimbine was observed, with some individuals exhibiting greatly increased oral bioavailability of yohimbine. Increases in blood pressure, respiratory rate, plasma catecholamine levels, and total VAS score were observed in participants with elevated AUC values. The AUC of yohimbine had the largest effect on total VAS score. The results indicate that higher doses of yohimbine are both well tolerated and produce dose-related increases in AUC, which are associated with more pronounced autonomic effects. Increases in respiratory rate and plasma MHPG appear to be the most reliable pharmacodynamic measures for single oral doses of yohimbine. Individual differences in the pharmacokinetics of yohimbine are important in determining pharmacodynamic effects and should be considered in evaluations of its clinical effectiveness.
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