Potential for Drug Interactions between Raltegravir and Metal-containingFormulations

摘要

Raltegravir (RAL) contains a beta-diketo acid scaffold, and binds Mg2+ ions by chelation at the active site of HTV integrase. Therefore, this motif can potentially bind polyvalent metals, and such interaction can occur if RAL is coadministered with a polyvalent metal-containing formulation. However, information about interactions between RAL and polyvalent metals is insufficient. The present in vitro study was conducted to obtain basic information about such interactions. One ISENTRESS~R (400 mg) Tablet alone or one ISENTRESS~R Tablet plus one tablet or one packet of a metal-containing formulation were suspended in water. The RAL content was measured by HPLC-UV, and the changes in color and pH of the suspensions were recorded. The content of RAL was decreased in comparison with the ISENTRESS~R Tablet alone when suspended simultaneously with a Magmitt~R (330 mg) Tablet, Calcium Lactate Hydrate (1g), Caltan~R (500 mg) Tablet, ULCERLMESf~R Fine Granule 90% (1g) or Ferromia~R (50 mg) Tablet. A significant color change was observed when the ISENTRESS~R Tablet was suspended simultaneously with a Ferromia"^ Tablet formulation, and a significant pH change was observed when the ISENTRESS~R Tablet was suspended simultaneously with a Magmitt~R Tablet or Caltan~R Tablet formulation. There was no apparent correlation between RAL content and the pH of the suspension. Interaction between RAL and some of the metal-containing formulations was confirmed in vitro. These results suggest that RAL may interact with metal-containing formulations in vivo. More detailed studies will be required to investigate the chemical structures formed between RAL and various metal cations, and the pharmacokinetics of these complexes.