TY - JOUR
T1 - Stereoselective monitoring of ± verapamil treatment of women with bipolar disorder
AU - Perel, J. M.
AU - Wisner, K. L.
AU - Rudolph, G.
AU - Peindl, K.
PY - 1999/1/1
Y1 - 1999/1/1
N2 - ±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.
AB - ±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.
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U2 - 10.1016/S0009-9236(99)80162-3
DO - 10.1016/S0009-9236(99)80162-3
M3 - Article
AN - SCOPUS:33749103195
SN - 0009-9236
VL - 65
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
IS - 2
ER -