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Clinical |
1 Department of Pediatric Nephrology and2 Department of Clinical Pharmacology, Children's Mercy Hospitals & Clinics, University of Missouri at Kansas City, Missouri; 3 Department of Pharmacy Practice, University of Florida, Gainesville, Florida;4 Albany College of Pharmacy, Albany, New York, USA
Correspondence to: D.L. Blowey, 2410 Gillham Road, Kansas City, Missouri 64108
USA.
dblowey{at}cmh.edu
Background: Little information is available on the
disposition of vancomycin during chronic peritoneal dialysis (PD) in children.
The primary objective of this study was to investigate the disposition of
vancomycin following intraperitoneal (IP) administration in children receiving
shortdwell [e.g., automated PD (APD)] and long-dwell [e.g., continuous
ambulatory PD (CAPD)] PD.
Methods: A 6-hour exchange containing vancomycin 500 mg/L,
using an exchange volume of 1100 mL/m2 body surface area (BSA), was
followed by 4-, 6-, and 8-hour antibiotic-free exchanges. The 8-hour exchange
was followed by three to four 90-minute antibiotic-free exchanges. Serial
blood and dialysis effluent samples were obtained and analyzed for vancomycin
concentration by high-pressure liquid chromatography. Pharmacokinetic
parameters were computed using noncompartmental methods.
Results: The bioavailability of vancomycin during a 6-hour
IP exchange was 70% ± 5%, resulting in a delivered dose of 12.0
± 1.8 mg/kg, and a 6-hour serum vancomycin concentration of 23.3
± 7.2 mmm g/mL. Total body vancomycin clearance measured 10.72 ±
4.52 mL/minute/1.73 m2 BSA, while clearance attributable to PD
measured 2.78 ± 1.08 mL/min/1.73 m2 BSA and accounted for
29% ± 11% of total vancomycin clearance. Dialysis clearance during
long-dwell (CAPD) and short-dwell (APD) regimens was similar, measuring 2.46
± 1.04 and 3.09 ± 1.28 mL/min/1.73 m2 BSA, accounting
for 25% ± 13% and 32% ± 12% of total body clearance
respectively.
Conclusions: Intraperitoneal absorption and dialysis
clearance of vancomycin in children receiving PD are similar to those reported
in adult dialysis patients. In contrast, total body clearance of vancomycin
appears to be increased and the elimination half-life decreased in children,
due to increased elimination by non-renal nondialysis routes. For intermittent
IP vancomycin therapy in children with peritonitis, an IP load containing
vancomycin 1000 mg/L (or 30 mg/kg), followed a single full-fill (1100
mL/m2 BSA) daily exchange, containing vancomycin 250 mg/L (or 7.5
mg/kg), from day 2 until the end of treatment will maintain a vancomycin
dialysate concentration of >4 µg/mL.
KEY WORDS: Vancomycin; pharmacokinetics; pediatric.
Received 22 December 2005; accepted 15 May 2006.
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