title: Nasogastric administration of garenoxacin as crushed tablets with and without concomitant enteral feeding in healthy subjects.
abstract: OBJECTIVE
  Cation-containing drugs have the potential to affect the absorption of quinolones. The current study was conducted to assess whether the bioavailability of garenoxacin was affected by administration as crushed tablets with and without concomitant enteral nutrition.
  
  
  METHODS
  This was a randomised, open-label, three-period, single-dose, crossover study carried out in healthy male volunteers who received study treatments at a clinical facility. The study included 18 subjects (mean age 30 +/- 6 years) who were treatment-naive to garenoxacin and had a body mass index of > or =18 kg/m(2) and < or =30 kg/m(2). Subjects received garenoxacin 600 mg orally in three treatments: (A) intact tablets; (B) crushed tablets suspended in water delivered via a nasogastric (NG) tube; and (C) treatment B plus concomitant enteral feeding (Osmolite; 600 mL at 100 mL/h). Serial plasma samples were collected post-dose for pharmacokinetic analysis. Pharmacokinetic parameters were determined by noncompartmental methods. Geometric mean ratio with 90% CI for area under the concentration-time curve from time 0 extrapolated to infinity (AUC(infinity)) and maximum observed plasma concentration (C(max)) were used to assess potential effects of the different conditions of administration. Absence of an effect was concluded if the 90% CIs for the ratio of geometric means for C(max) and AUC(infinity) were within 0.7-1.43 and 0.8-1.25, respectively. The pharmacokinetics (AUC(infinity)and C(max)) and safety of garenoxacin were assessed.
  
  
  RESULTS
  Geometric means for C(max) were 8.3, 8.5 and 8.3 microg/mL and for AUC(infinity) were 103.3, 97.2 and 93.4 microg.h/mL for treatments A, B and C, respectively. The 90% CIs for geometric mean ratios for AUC(infinity) and C(max) of garenoxacin administered as crushed tablets and crushed tablets with Osmolite via NG tube relative to intact tablets administered orally were within 0.80-1.25, suggesting that the bioavailability of garenoxacin was not affected by delivery of crushed tablets via NG tube, regardless of concomitant enteral feeding, compared with oral delivery of intact tablets. Half-life (mean range 12-13 hours) was similar for all three groups.
  
  
  CONCLUSIONS
  The relative bioavailability of garenoxacin was not affected by administration as crushed tablets, regardless of enteral feeding. Garenoxacin can be administered as crushed tablets in the presence or absence of concomitant Osmolite.
authors.affiliation: Department of Pharmacokinetic and Early Clinical Research & Experimental Medicine, Schering-Plough Research Institute, Kenilworth, New Jersey, USA. Gopal.Krishna@spcorp.com
authors.forename: Gopal
authors.initials: G
authors.lastname: Krishna
authors.forename: Robert
authors.initials: R
authors.lastname: Noveck
authors.forename: Ramon
authors.initials: R
authors.lastname: Vargas
authors.forename: Dennis
authors.initials: D
authors.lastname: Grasela
authors.forename: Zaiqi
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D015992:Body Mass Index; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D004750:Enteral Nutrition / Q000379:methods*; D024841:Fluoroquinolones / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007441:Intubation, Gastrointestinal; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D011208:Powders; D012044:Regression Analysis; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D011208:Powders; D013607:Tablets; C419689:garenoxacin