TY - JOUR
T1 - Thiothixene pharmacokinetic interactions
T2 - A study of hepatic enzyme inducers, clearance inhibitors, and demographic variables
AU - Ereshefsky, Larry
AU - Saklad, Stephen R.
AU - Watanabe, Mark D.
AU - Davis, Chester M.
AU - Jann, Michael W.
PY - 1991/10
Y1 - 1991/10
N2 - Fifty-nine plasma thiothixene concentrations were measured in 42 patients as part of routine therapeutic drug monitoring. Data collection included concomitant medications, smoking history, and demographic variables. A retrospective analysis was performed to assess the effect of these parameters on oral thiothixene clearance. When groups of patients were categorized by concomitant medications (i.e., no interacting drugs, enzyme/clearance inducers, and enzyme/clearance inhibitors), thiothixene clearance was found to be significantly increased by enzyme inducing drugs (e.g., anticonvulsants) and decreased by clearance inhibiting agents (e.g., cimetidine). Tobacco smoking significantly increased the hepatic clearance of thiothixene within the no interactions and inhibitor groups, but not in the inducer group. Significantly more patients in the inducer group had nondetectable plasma concentrations of thiothixene than the other groups. When the entire patient population was dichotomized by age, patients > 50 years old had a significantly greater mean clearance (48.2 ± 37.8 liters/min) versus those ≥ 50(20.0 ± 12.6 liters/min). Men in this cohort exhibited a significantly higher clearance (49.2 ± 38.7 liters/min) than did the women (22.0 ± 13.5 liters/ min). By taking into account these potential sources of pharmacokinetic variability when monitoring plasma thiothixene concentrations, more appropriate dosing of thiothixene may be achieved. Controlled, prospective studies are needed to validate these findings.
AB - Fifty-nine plasma thiothixene concentrations were measured in 42 patients as part of routine therapeutic drug monitoring. Data collection included concomitant medications, smoking history, and demographic variables. A retrospective analysis was performed to assess the effect of these parameters on oral thiothixene clearance. When groups of patients were categorized by concomitant medications (i.e., no interacting drugs, enzyme/clearance inducers, and enzyme/clearance inhibitors), thiothixene clearance was found to be significantly increased by enzyme inducing drugs (e.g., anticonvulsants) and decreased by clearance inhibiting agents (e.g., cimetidine). Tobacco smoking significantly increased the hepatic clearance of thiothixene within the no interactions and inhibitor groups, but not in the inducer group. Significantly more patients in the inducer group had nondetectable plasma concentrations of thiothixene than the other groups. When the entire patient population was dichotomized by age, patients > 50 years old had a significantly greater mean clearance (48.2 ± 37.8 liters/min) versus those ≥ 50(20.0 ± 12.6 liters/min). Men in this cohort exhibited a significantly higher clearance (49.2 ± 38.7 liters/min) than did the women (22.0 ± 13.5 liters/ min). By taking into account these potential sources of pharmacokinetic variability when monitoring plasma thiothixene concentrations, more appropriate dosing of thiothixene may be achieved. Controlled, prospective studies are needed to validate these findings.
UR - http://www.scopus.com/inward/record.url?scp=0025833549&partnerID=8YFLogxK
M3 - Article
C2 - 1765572
AN - SCOPUS:0025833549
SN - 0271-0749
VL - 11
SP - 296
EP - 301
JO - Journal of Clinical Psychopharmacology
JF - Journal of Clinical Psychopharmacology
IS - 5
ER -