title: Population pharmacokinetic and pharmacodynamic modeling of acetazolamide in peritoneal dialysis patients and healthy volunteers.
abstract: OBJECTIVE
  To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of acetazolamide (ACTZ) in peritoneal dialysis patients, ACTZ 500 mg was administered intravenously to 7 healthy subjects (HV) and 8 peritoneal dialysis patients (CAPD).
  
  
  METHODS
  Population PK/PD modeling was performed with ACTZ serum (total and unbound), urine and dialysate concentrations, intra-ocular pressure (IOP) and covariates. A multi-compartment PK model (accounting for non-linear protein binding) and an inhibitory Emax (maximal change in IOP) PD model were selected.
  
  
  RESULTS
  As expected, renal clearance (which almost equals total body clearance) was severely decreased in CAPD (1.2 vs 80.3 L/h) and the elimination half-life of total ACTZ was prolonged (20.6 vs 3.4 hours). The protein binding was significantly altered with a mean free fraction 4.2% in HV and 8.6% in CAPD. Moreover protein binding of ACTZ was concentration dependent in both HV and CAPD. Despite a higher free fraction of ACTZ, the Emax was lower in CAPD: 4.4±1.4 vs 7.4±2.8 mmHg.
  
  
  CONCLUSIONS
  Both PK and PD are significantly altered in dialysis patients.
authors.affiliation: Faculty of Pharmacy, University of Montreal, Canada.
authors.forename: Corinne Seng
authors.initials: CS
authors.lastname: Yue
authors.forename: Huu Hung
authors.initials: HH
authors.lastname: Huynh
authors.forename: Catherine
authors.initials: C
authors.lastname: Raymond
authors.forename: Louise
authors.initials: L
authors.lastname: Charbonneau
authors.forename: Louise
authors.initials: L
authors.lastname: Roy
mesh_terms: D000086:Acetazolamide / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D000328:Adult; D001798:Blood Proteins / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010530:Peritoneal Dialysis; D011485:Protein Binding; D055815:Young Adult
chemical_list: D001798:Blood Proteins; D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide