title: Population pharmacokinetics of clindamycin orally and intravenously administered in patients with osteomyelitis.
abstract: OBJECTIVE
  This study was performed to describe clindamycin, administered either orally or intravenously, concentration-time courses to patients with osteomyelitis, to study the effects of different covariates on clindamycin pharmacokinetics and to simulate an optimized administration scheme.
  
  
  METHODS
  Clindamycin concentrations were measured in 50 patients. A total of 122 plasma concentrations were available (58 from oral administration and 64 from i.v. infusion). A population pharmacokinetic model was developed with MONOLIX 4 software.
  
  
  RESULTS
  A one compartment model adequately described the data. Clindamycin clearance increased significantly with body weight (BW). The typical population estimates (interindividual variability) for clearance, volume of distribution and absorption rate constant were 16.2 l h(-1) (0.39), 70.2 l and 0.92 h(-1) , respectively. The bioavailability of the oral form was estimated to be 87.6%. According to BW, theoretical doses needed to reach a C(min) of 2 mg l(-1) were then calculated.
  
  
  CONCLUSIONS
  The current recommendation of 600 mg three times daily seems to be effective up to 75 kg but the dose should be raised to 900 mg three times daily thereafter. These assumptions should be prospectively confirmed.
authors.affiliation: EA 3620, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. naim.bouazza@cch.aphp.fr
authors.forename: Naïm
authors.initials: N
authors.lastname: Bouazza
authors.forename: Vincent
authors.initials: V
authors.lastname: Pestre
authors.forename: Vincent
authors.initials: V
authors.lastname: Jullien
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Curis
authors.forename: Saïk
authors.initials: S
authors.lastname: Urien
authors.forename: Dominique
authors.initials: D
authors.lastname: Salmon
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Tréluyer
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D001835:Body Weight; D002981:Clindamycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D010019:Osteomyelitis / Q000188:drug therapy / Q000378:metabolism*; D012189:Retrospective Studies; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D002981:Clindamycin; D012293:Rifampin