Open AccessConcurrent administration with multivalent metal cation preparations or polycationic polymer preparations inhibits the absorption of raltegravir via its chelation
Author(s) -
Enoki Yuki,
Suzuki Norihiro,
Ito Motoyasu,
Uchiyama Eri,
Kishi Nagomi,
Ito Chihiro,
Kitahiro Yuki,
Sakamoto Kazuki,
Taguchi Kazuaki,
Yokoyama Yuta,
Kizu Junko,
Matsumoto Kazuaki
Publication year - 2020
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.13330
Subject(s) - chemistry , isothermal titration calorimetry , metal , chelation , polymer , enthalpy , pharmacokinetics , absorption (acoustics) , dendrimer , nuclear chemistry , inorganic chemistry , polymer chemistry , organic chemistry , pharmacology , biochemistry , medicine , physics , quantum mechanics , acoustics
Objectives Raltegravir (RAL) that can form chelates with multivalent metal cations shows lateral interactions with multivalent metal cation and polycationic polymer. We investigated the interactions of RAL with multivalent metal cation preparations, Al(OH) 3 and LaCO 3 , and polycationic polymer preparations, bixalomer (Bxl) and sevelamer (Svl). Methods Immediately before the oral administration of 40 mg/kg RAL, the rats were administered orally with the vehicle, Al(OH) 3 , LaCO 3 , Bxl, or Svl, and the time course of RAL serum concentration was followed. The in vitro binding affinity of RAL with multivalent metal cation and polycationic polymer was also evaluated using isothermal titration calorimetry (ITC). Results When Al(OH) 3 , LaCO 3 , Bxl, or Svl was concomitantly administered with RAL, the maximum concentration and area under the curve were significantly lower than those when RAL was administered alone. ITC showed the interaction of RAL with Al(OH) 3 as an enthalpy‐driven reaction and its interactions with LaCO 3 and Bxl as entropy–enthalpy mixed reactions. Conclusions The interaction of RAL with Al(OH) 3 , LaCO 3, Bxl, or Svl can inhibit RAL absorption into the gastrointestinal tract, and thus, the multivalent metal cation and polycationic polymer are the modifying factors that can affect RAL pharmacokinetics.