Ferrous sulphate interacts with captopril

AIMS: To determine if iron binds strongly to captopril and reduces captopril absorption. METHODS: A variety of in vitro experiments was conducted to examine iron binding to captopril and a randomized, double-blind, placebo controlled, cross-over study design was used to assess the in vivo interaction. Captopril (25 mg) was coingested with either ferrous sulphate (300 mg) or placebo by seven healthy adult volunteers. Subjects were phlebotomized and had blood pressure measured at 0, 0.25, 0.5, 1, 2, 4, 6, 8, and 12 h post ingestion. A 1 week washout period was used. RESULTS: The coingestion of ferrous sulphate and captopril was associated with a 37% (134 ng ml(-1) h, 95% CI 41-228 ng ml(-1) h, P = 0.03) decrease in area under the curve (AUC) for unconjugated plasma captopril. There were no substantial changes in Cmax (mean difference; -32; 95% CI -124-62 ng ml(-1) (P = 0.57)) or in tmax (mean difference; 0; 95% CI -18-18 min (P = 0.65)) for unconjugated captopril when captopril was ingested with iron. There was a statistically insignificant increase in AUC for total plasma captopril of 43% (1312 ng ml(-1) h, 95% CI -827-3451 ng ml(-1) h P = 0.27) when captopril was ingested with iron. The addition of ferric chloride to captopril resulted in the initial rapid formation of a soluble blue complex which rapidly disappeared to be replaced by a white precipitant. The white precipitate was identified as captopril disulphide dimer. There were no significant differences in systolic and diastolic blood pressures between the treatment and placebo groups. CONCLUSIONS: Co-administration of ferrous sulphate and iron results in decreased unconjugated captopril levels likely due to a chemical interaction between ferric ion and captopril in the gastrointestinal tract. Care is required when coprescribing captopril and iron salts.