title: Determination of renal tissue ibandronate levels in rats with normal and mildly impaired renal function.
abstract: BACKGROUND
  After entering the blood, bisphosphonates are immediately bound to bone or excreted unchanged by the kidney. During renal excretion about 0.5% of administrated dosage remains in kidney tissue. The renal tissue level of bisphosphonates (RTL) decreases over time and remains at about 0.15% after 3weeks, but the influence of renal insufficiency (RI) is unclear.
  
  
  METHODS
  We investigated the influence of mild to moderate RI on RTL of ibandronate (IBD). First a method for determination of RTL was implemented and validated. We measured RTL in rats with normal renal function (SHAM) and after unilateral nephrectomy (UNX). In each case one SHAM and one UNX groups received one or alternatively 9 times every 3weeks a dosage of 1.5mg/kg IBD. After the last dosage the rats were sacrificed and RTL of IBD were determined.
  
  
  RESULTS
  In SHAM-rats IBD concentrations increased from 272.7ng/g kidney after one injection to 428.9ng/g kidney after nine injections (p<0.0001). RTL in UNX rats likewise increased significantly (p<0.0001) from 289.9ng/g kidney to 520.2ng/g kidney.
  
  
  CONCLUSIONS
  Our study found a 1.6 fold increase of RTL in SHAM rats and a 1.8 fold increase of RTL in UNX rats after nine versus one injection. As steady state is generally reached after five half-lives we anticipate no further accumulation on continued treatment.
authors.affiliation: Medical Department A, Klinikum der Stadt Ludwigshafen, Ludwigshafen, Germany. Electronic address: bergnerr@klilu.de.
authors.forename: R
authors.initials: R
authors.lastname: Bergner
authors.affiliation: Department of Pharmacy, University Medical Center of the Johannes Gutenberg University Mainz, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Siegrist
authors.affiliation: Zentrum für Medizinische Forschung, Medizinische Fakultät Mannheim, Ruprecht-Karls University, Mannheim, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Kränzlin
authors.affiliation: Zentrum für Medizinische Forschung, Medizinische Fakultät Mannheim, Ruprecht-Karls University, Mannheim, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Gretz
authors.affiliation: Celerion Switzerland AG, Fehraltorf, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Faust
authors.affiliation: Hoffmann-La Roche, Ltd Group Safety, Security and Environmental Protection, Basel, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Pfister
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004164:Diphosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D005260:Female; D006207:Half-Life; D000077557:Ibandronic Acid; D007668:Kidney / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000503:physiopathology*; D012720:Severity of Illness Index; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000077557:Ibandronic Acid