L-thyroxine contamination of pharmaceutical D-thyroxine: probable cause of therapeutic effect.
Studies have shown that pharmaceutic preparations of the stereo isomers of thyroxine differ with respect to thyromimetic potency and lipid level-lowering effects. We applied a stereospecific assay for dextrothyroxine (DT4) and levothyroxine (LT4) to determine whether the biologic effects observed after the administration of DT4 (Choloxin; Flint Laboratories) resulted from inherent biologic activity of DT4, conversion of DT4 to LT4 in vivo, or LT4 contamination of Choloxin tablets. Choloxin was administered in a dose of 8 mg/day for 5 mo to nine athyreotic subjects who were then treated with pharmaceutic LT4 (Synthroid), 0.2 mg/day for an additional 5 mo. Analysis showed that LT4 contamination of Choloxin tablets ranged from 0.50% to 2.30%. This degree of contamination resulted in physiologically significant doses of LT4 in the 8 mg/day doses of Choloxin. During the treatment with two different lots of Choloxin, serum LT4 accounted for 33% to 53% of the measurable serum total thyroxine. The degree of LT4 contamination in Choloxin tablets was sufficient to account for the observed serum LT4 levels and casts doubt on the conclusions derived from previous studies in which Choloxin was used as the source of "DT4."
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002784:Cholesterol / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003918:Dextrothyroxine / Q000032:analysis* / Q000627:therapeutic use; D004340:Drug Contamination; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D013237:Stereoisomerism; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000032:analysis* / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D014280:Triglycerides; D003918:Dextrothyroxine; D013972:Thyrotropin; D002784:Cholesterol; D013974:Thyroxine