FERROUS SULFATE INTERACTS WITH CAPTOPRIL

Aims To determine if iron binds strongly to captopril and reduces capt opril absorption. Methods A variety of in vitro experiments was conduc ted to examine iron binding to captopril and a randomized, double-blin d, placebo controlled, cross-over study design was used to assess the in vivo interaction. Captopril (25 mg) was coingested with either ferr ous sulphate (300 mg) or placebo by seven healthy adult volunteers. Su bjects were phlebotomized and had blood pressure measured at 0, 0.25, 0.5, 1, 2, 1, 6, 8, and 12 h post ingestion. A 1 week washout period w as 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 c aptopril. There were no substantial changes in C-max (mean difference; -32; 95% CI - 124-62 ng ml(-1) (P=0.57)) or in t(max) (mean difference ; 0; 95% CI -18-18 min (P=0.65)) for unconjugated captopril when capto pril was ingested with iron. There was a statistically insignificant i ncrease 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 ir on. The addition of ferric chloride to captopril resulted in the initi al rapid formation of a soluble blue complex which rapidly disappeared to be replaced by a white precipitant. The white precipitate was iden tified as captopril disulphide dimer. There were no significant differ ences in systolic and diastolic blood pressures between the treatment: and placebo groups. Conclusions Go-administration of ferrous sulphate and iron results in decreased unconjugated captopril levels Likely du e to a chemical interaction between ferric ion and captopril in the ga strointestinal tract. Care is required when coprescribing captopril an d iron salts.