Plasma tranylcypromine: relationship to pharmacokinetic variables and clinical antidepressant actions.
Because the clinical actions of psychotherapeutic agents can be influenced by their pharmacokinetics, we investigated plasma tranylcypromine in relation to treatment outcome in 26 patients with bipolar depression. After oral administration of a tranylcypromine dose, plasma drug levels were measured hourly from 5-8 hours (N = 16) or 0-8 hours (N = 10) postdose, and pharmacokinetic parameters were calculated. Depressive symptoms were rated using the Hamilton Rating Scale for Depression (HAM-D), and subjects were categorized as responders, partial responders, or nonresponders, based on end-pair ratings. Twelve subjects were responders, seven were partial responders, and seven were nonresponders (mean scores = 3.2, 13.1, and 24.9, respectively); pretreatment HAM-D scores did not differ among the three groups. Tranylcypromine elimination (t1/2) was unrelated to clinical outcome. However, plasma tranylcypromine measured 5 hours postdose (5hTCP) was correlated with the end-pair HAM-D scores (r = 0.48, p less than 0.015) and was significantly higher in nonresponders than in responders (ANOVA, F = 4.7, p less than 0.02; Newman-Keuls test, p less than 0.05). For subjects who were studied from 0-8 hours postdose, the time to peak absorption (Tpeak), the area under the plasma tranylcypromine-versus-time curve, and the volume of distribution (Vd) were determined. Two subjects having delayed (3-4 hours) Tpeak also manifested elevated mean 5hTCP (63.9 vs. 34.1 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Mallinger
A G
AG
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pennsylvania.
Himmelhoch
J M
JM
Thase
M E
ME
Edwards
D J
DJ
Knopf
S
S
D000328:Adult; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy; D003866:Depressive Disorder / Q000097:blood* / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D011569:Psychiatric Status Rating Scales; D014018:Tissue Distribution / Q000502:physiology; D014191:Tranylcypromine / Q000008:administration & dosage / Q000493:pharmacokinetics*
D014191:Tranylcypromine