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 (DT 4 ) and levothyroxine (LT 4 ) to determine whether the biologic effects observed after the administration of DT 4 (Choloxin; Flint Laboratories) resulted from inherent biologic activity of DT 4 , conversion of DT 4 to LT 4 in vivo, or LT 4 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 LT 4 (Synthroid), 0.2 mg/day for an additional 5 mo. Analysis showed that LT 4 contamination of Choloxin tablets ranged from 0.50% to 2.30%. This degree of contamination resulted in physiologically significant doses of LT 4 in the 8 mg/day doses of Choloxin. During the treatment with two different lots of Choloxin, serum LT 4 accounted for 33% to 53% of the measurable serum total thyroxine. The degree of LT 4 contamination in Choloxin tablets was sufficient to account for the observed serum LT 4 levels and casts doubt on the conclusions derived from previous studies in which Choloxin was used as the source of “DT 4 .” Clinical Pharmacology and Therapeutics (1984) 36 , 781–787; doi: 10.1038/clpt.1984.257