±Verapamil (Ver) appears to be promising for the treatment of bipolar disorder and is safer in pregnancy. We are currently undertaking a comparative, double-blind, random assignment efficacy study of ±Verapamil and Lithium. Target oral dosage (immediate release) of the ±Ver cell ranges from 160-480 mg/d. Here, we report stereoselective pilot data on 19 mid-life female patients. The analyses are with HPLC/fluorescence detection utilizing an Astec chirobiotic V column. The enantiomers of ±Ver and ±NorVer are separated, R:44.1, S:46.7 and I.S. (S-propranolol):31.6, R:67.9 and S:76.5min, respectively; detectability: 2.5-5.ng/ml. Analogously to reported cardiovascular literature, we have found major differences of stereoselective metabolism. The plasma S/R ratio for ±Ver is 0.22±0.03 (S.D.) And ±NorVer is 0.37±0.03 (S.D.). The S-forms for both ±Ver and ±NorVer, also appear to be more active for bipolar symptom amelioration, and are eliminated 2-5 times faster leading to much lower S plasma levels. For optimal therapeutic outcome, plasma level monitoring of the individual enantiomers would appear to be necessary.
ASJC Scopus subject areas
- Pharmacology (medical)