Yohimbine elimination in normal volunteers is characterized by both one- and two-compartment behavior.
We sought to determine the safety, pharmacodynamic response, and single- and multiple-dose pharmacokinetic profile of yohimbine hydrochloride. Thirty-two healthy volunteers received 6 days of yohimbine, 5.4 mg 3 times daily (t.i.d.), 10.8 mg t.i.d., 16.2 mg t.i.d., or 21.6 mg twice daily (b.i.d.), with determination of plasma catecholamine levels and mood/anxiety-inventory scores. The pharmacokinetic profile of yohimbine was determined after the first and last dose. Yohimbine exhibited one-compartment elimination in most subjects, with dose-dependent increases in maximal concentration (Cmax) and area under the curve (AUC) but no evidence of drug accumulation. At least two subjects in each cohort exhibited two-compartment elimination of yohimbine, with nonsignificant increases in day 7 AUC, Cmax, and terminal elimination half-life (t1/2beta). Plasma catecholamine levels increased significantly in relation to both average yohimbine AUC and Cmax, but there were no significant effects on heart rate, blood pressure, or anxiety/mood-inventory scores. The single- and multiple-dose pharmacokinetic profile of yohimbine exhibits a substantial degree of interpatient and intrapatient variability, possibly resulting from variability in first-pass and hepatic metabolism. There is a significant correlation between plasma norepinephrine levels and yohimbine AUC or Cmax. Further multiple-dose studies are warranted definitively to address the relation between yohimbine AUC or Cmax and pharmacologic effect.
Sturgill
M G
MG
University of Medicine and Dentistry of New Jersey (UMDNJ)-Robert Wood Johnson Medical School, New Brunswick 08903-0019, USA.
Grasing
K W
KW
Rosen
R C
RC
Thomas
T J
TJ
Kulkarni
G D
GD
Trout
J R
JR
Maines
M
M
Seibold
J R
JR
D000328:Adult; D000339:Affect / Q000187:drug effects; D001007:Anxiety / Q000139:chemically induced; D019540:Area Under Curve; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood; D006207:Half-Life; D006801:Humans; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000097:blood; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010555:Personality Inventory; D015016:Yohimbine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
D015016:Yohimbine; D008734:Methoxyhydroxyphenylglycol; D009638:Norepinephrine; D004837:Epinephrine