title: How to calculate clearance of highly protein-bound drugs during continuous venovenous hemofiltration demonstrated with flucloxacillin.
abstract: BACKGROUND
  Flucloxacillin is an important antimicrobial drug in the treatment of infections with Staphylococcus aureus and therefore is often used in staphylococcal infections. Furthermore, flucloxacillin has a high protein binding rate as for example ceftriaxone or teicoplanin--drugs which have formerly been characterized as not being dialyzable.
  
  
  METHODS
  The pharmacokinetic parameters of 4.0 g flucloxacillin every 8 h were examined in 10 intensive care patients during continuous venovenous hemofiltration (CVVH) using a polyamide capillary hemofilter. In addition, the difficulty of calculating the hemofiltration clearance of a highly protein-bound drug is described.
  
  
  RESULTS
  Flucloxacillin serum levels were significantly lowered (56.9 +/- 24.0%) even though only 15% of the drug was detected in the ultrafiltrate. Elimination half-life, total body clearance and sieving coefficient were 4.9 +/- 0.7 h, 117.2 +/- 79.1 ml/min and 0.21 +/- 0.09, respectively. These discrepancies can be explained by the high protein binding of flucloxacillin, the adsorbing property of polyamide and the equation in order to calculate hemofiltration clearance. The unbound fraction of a 4.0 g flucloxacillin dosage facilitates time above the minimum inhibitory concentration (T > MIC) of 60% only for strains up to a minimum inhibitory concentration (MIC) of 0.5 mg/l.
  
  
  CONCLUSIONS
  Based on the data of this study, we conclude that intensive care patients with staphylococcal infections on CVVH should be treated with 4.0 g flucloxacillin every 8 h which was safe and well tolerated. Moreover, further studies with highly protein-bound drugs are recommended to check the classical 'hemodialysis' equation as the standard equation in calculating the CVVH clearance of highly protein-bound drugs.
authors.affiliation: Department of Internal Medicine I, Division of Infectious Diseases, University of Vienna, Vienna, Austria.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Meyer
authors.forename: Salwa
authors.initials: S
authors.lastname: Ahmed el Gendy
authors.forename: Georg
authors.initials: G
authors.lastname: Delle Karth
authors.forename: Gottfried J
authors.initials: GJ
authors.lastname: Locker
authors.forename: Gottfried
authors.initials: G
authors.lastname: Heinz
authors.forename: Walter
authors.initials: W
authors.lastname: Jaeger
authors.forename: Florian
authors.initials: F
authors.lastname: Thalhammer
mesh_terms: D000368:Aged; D019540:Area Under Curve; D003422:Critical Care; D005260:Female; D005436:Floxacillin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006207:Half-Life; D006440:Hemofiltration; D006801:Humans; D008297:Male; D008875:Middle Aged; D010406:Penicillins / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011485:Protein Binding; D015610:Serum Bactericidal Test; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000378:metabolism
chemical_list: D010406:Penicillins; D005436:Floxacillin