title: Development of hemiacetal esterified levofloxacin to prevent chelation with metal-containing drugs.
abstract: OBJECTIVE
  To avoid the chelate formation between levofloxacin (LVFX) and aluminium hydroxide in gastrointestinal tract, an ethoxycarbonyl 1-ethyl hemiacetal ester of levofloxacin (LVFX-EHE) was synthesised as a prodrug.
  
  
  METHODS
  The effects of aluminium hydroxide on the bioavailability of LVFX following oral administration of LVFX-EHE were investigated in rats. Furthermore, the effects of aluminium hydroxide on small intestinal absorption of LVFX and LVFX-EHE when subjected to a hydrolysis experiment using in situ everted gut sac were investigated, and the minimal inhibitory concentrations (MICs) of LVFX and LVFX-EHE for various intestinal bacteria were measured.
  
  
  RESULTS
  When LVFX-EHE was co-administered with and without aluminium hydroxide, the AUC0-4 hvalues of LVFX hydrolysed from LVFX-EHE were similar to that of LVFX alone. In everted gut sac experiments, LVFX-EHE was efficiently absorbed even in the presence of aluminium ions after 1 h of incubation, whereas the absorption of LVFX decreased significantly in the presence of aluminium ions. MIC values of LVFX-EHE were far higher than LVFX.
  
  
  CONCLUSIONS
  This study suggests the benefit of ethoxycarbonyl 1-ethyl hemiacetal esterification of the carboxyl group of new quinolone as a prodrug which is able to avoid chelate formation.
authors: Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan.
authors: Toru
authors: T
authors: Otori
authors: Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan.
authors: Sumio
authors: S
authors: Matzno
authors: Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan.
authors: Atushi
authors: A
authors: Kawase
authors: Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan.
authors: Masahiro
authors: M
authors: Iwaki
authors: School of Pharmacy, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.
authors: Tetsutaro
authors: T
authors: Kimachi
authors: Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan.
authors: Keiji
authors: K
authors: Nishiwaki
authors: Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan.
authors: William C
authors: WC
authors: Figoni
authors: Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan.
authors: Ryuta
authors: R
authors: Tominaga
authors: Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan.
authors: Mai
authors: M
authors: Asahide
authors: Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan.
authors: Mayumi
authors: M
authors: Nishikata
authors: School of Pharmacy, Toho University, Funabashi, Chiba, Japan.
authors: Yoshikazu
authors: Y
authors: Ishii
authors: Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan.
authors: Kenji
authors: K
authors: Matsuyama
mesh_terms: D000284:Administration, Oral; D000536:Aluminum Hydroxide / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D001682:Biological Availability; D002614:Chelating Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D004339:Drug Compounding; D004347:Drug Interactions; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism / Q000382:microbiology; D064704:Levofloxacin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D008297:Male; D008826:Microbial Sensitivity Tests; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D017207:Rats, Sprague-Dawley
chemical_list: D000900:Anti-Bacterial Agents; D002614:Chelating Agents; D011355:Prodrugs; C000618840:levofloxacin ethoxycarbonyl 1-ethyl hemiacetal ester; D000536:Aluminum Hydroxide; D064704:Levofloxacin
keywords: chelate; hemiacetal ester; prodrug