Clearance of vancomycin during high-efficiency hemodialysis.
BACKGROUND
Vancomycin is commonly used for the treatment of MRSA infections in critically ill patients with renal diseases. Vancomycin is mainly eliminated through the kidney. Its excretion is therefore substantially reduced in severe renal impaired patients. Although several studies have demonstrated that significant amounts of vancomycin are removed during High-Flux/High-Efficiency Hemo Dialysis (HF/HEHD), more data are required to optimize clinical applications.


OBJECTIVE
Predict the appropriate vancomycin intradialytic dosage and dosing interval among patients receiving HEHD.


METHODS
Twenty patients who were receiving HEHD with cellulose triacetate dialyzer were included to determine the vancomycin intradialytic clearance. Two patients were included twice and one patient was included three times due to reinfections. This gave rise to 24 patient-times. The study was carried out at Songklanagarind Hospital between January 2003 and March 2004.


RESULTS
In a prospective opened label design, each patient received 1g vancomycin, 1 hour infusion, immediately after completion of HEHD. Six scheduled blood samples were drawn as follows: (1) 60 minutes following completion of vancomycin infusion (Cmax); (2) immediately before starting the second HEHD; (3) 2 hours after starting the second HEHD; (4) immediately after completion of the second HEHD; (5) immediately before starting the third HEHD; and (6) immediately after the third HEHD ended (Cmin). The authors measured vancomycin serum levels using HPLC technique. The serum concentrations were used to calculate all relevant pharmacokinetic parameters. The pharmacokinetic parameters (mean +/- SD) were: intradialytic clearance (CLHD) 93.4 +/- 37.1 mL/min; intradialytic elimination rate constant (k) 1.1 +/- 0.5 hr(-1); overall elimination half-life (t(1/2)) 77.1 +/- 37.8 hr; volume of distribution (Vd) 82.1 +/- 40.3 L; Cmax 25.8 +/- 8.12 mg/L (range 12.04-48.80); Cmin 6.2 +/- 3.1 mg/L; and % removal during the second HEHD 37.9 +/- 12.9. Subtherapeutic levels were found in 66.7% (16/24) and 91.6% (22/24) of patients after the second and the third HEHD, respectively.


CONCLUSIONS
HEHD with cellulose triacetate dialyzer removes significant amount of vancomycin. Based on the authors' findings, a loading dose of 1 g, and 500 mg after every subsequent HEHD is recommended.
Klansuwan
Nattha
N
Department of Pharmacy, Sadao Hospital, Songkhla.
Ratanajamit
Chaveewan
C
Kasiwong
Srirat
S
Wangsiripaisan
Adisorn
A
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002482:Cellulose / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012044:Regression Analysis; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000628:therapy*; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D014640:Vancomycin; D002482:Cellulose; C024671:cellulose triacetate