Effects of ascorbic acid on interactions between ciprofloxacin and ferrous sulphate, sodium ferrous citrate or ferric pyrophosphate, in mice

The absorption of ciprofloxacin has been reported to be impaired by concomitant administration of ferrous sulphate. The effects of sodium ferrous citrate and ferric pyrophosphate, which have been used as extensively as ferrous sulphate, on the absorption of ciprofloxacin were compared with that of ferrous sulphate. The effects of ascorbic acid on the interactions between ciprofloxacin and each iron compound were studied in mice. Mice were treated orally with ciprofloxacin (50mg kg(-1)) alone, the iron compound (ferrous sulphate, sodium ferrous citrate or ferric pyrophosphate; 50 mg elemental iron kg(-1)) alone, ciprofloxacin with each iron compound or ciprofloxacin in combination with each iron compound and ascorbic acid (250 mg kg(-1)). The maximum serum concentration of ciprofloxacin was significantly (P < 0.01) reduced from 1.15+/-0.11 mu g mL(-1) (ciprofloxacin alone) to 0.17+/-0.01, 0.27+/-0.01 or 0.28+/-0.02 mu g mL(-1), respectively, when ferrous sulphate, sodium ferrous citrate or ferric pyrophosphate was administered along with ciprofloxacin. The addition of ascorbic acid did not affect the inhibitory effects of each iron compound on the absorption of ciprofloxacin. Ciprofloxacin did not affect the variation of serum iron levels after administration of each iron compound. The addition of ascorbic acid significantly (P < 0.01) enhanced the increase in serum iron concentration after administration of sodium ferrous citrate, showing an increase from 270+/-6 mu g dL(-1) to 463+/-11 mu g dL(-1) compared with an increase from 248+/-8 mu g dL(-1) to 394+/-18 mu g dL(-1) after administration of sodium ferrous citrate alone. Ascorbic acid also caused a significant (P < 0.01) increase in serum iron concentration from 261+/-16 mu g dL(-1) to 360+/-12 mu g dL(-1) after administration of ferric pyrophosphate, although it did not affect the levels after ferrous sulphate administration. The results suggest that sodium ferrous citrate and ferric pyrophosphate should not be administered with ciprofloxacin (as for ferrous sulphate) and that sodium ferrous citrate is converted to the ferric form more easily than ferrous sulphate. This difference in convertibility might contribute to a clinical difference between sodium ferrous citrate and ferrous sulphate.