Pharmacokinetics of intraperitoneal gentamicin in peritoneal dialysis patients with peritonitis (GIPD study).
OBJECTIVE
Peritonitis is a major infectious complication in peritoneal dialysis patients, and intraperitoneal antibiotic administration is preferred to ensure maximal antibiotic concentrations at the site of infection. This study aimed to describe the plasma and infection site pharmacokinetics of intraperitoneal gentamicin in patients with peritonitis.


METHODS
This prospective pharmacokinetic study of intraperitoneal gentamicin was conducted in peritoneal dialysis patients presenting to hospital with clinically defined signs and symptoms of peritonitis. Twenty-four patients were administered a 0.6-mg/kg dose of intraperitoneal gentamicin, which was allowed to dwell for 6 hours. Serial blood and dialysate samples were collected for 24 hours after the first dose. Gentamicin concentrations in plasma and dialysate were measured using a validated assay.


RESULTS
The median percentage of the dose absorbed into the systemic circulation was 76% (interquartile range=69%-82%) and significantly different between patients with low average, high average, and high peritoneal membrane transporter status (P=0.03). The calculated pharmacokinetic parameters were plasma terminal elimination half-life of 24.7 (20.4-29.9) hours, terminal volume of distribution of 0.30 (0.20-0.36) L/kg, observed peak plasma concentration of 3.1 (2.4-3.4) mg/L, and observed trough plasma concentration of 1.9 (1.4-2.2) mg/L. The peak gentamicin concentration in dialysate was at least eight times the minimum inhibitory concentration of the likely pathogens.


CONCLUSIONS
The high systemic absorption of gentamicin in patients with peritonitis and prolonged plasma elimination half-life may lead to drug accumulation in the systemic circulation, increasing the risk of toxicity.
Burns, Trauma & Critical Care Research Centre, The University of Queensland, Brisbane, Australia. j.varghese1@uq.edu.au
Julie M
JM
Varghese
Jason A
JA
Roberts
Steven C
SC
Wallis
Robert J
RJ
Boots
Helen
H
Healy
Robert G
RG
Fassett
Jeffrey
J
Lipman
Dwarakanathan
D
Ranganathan
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016903:Drug Monitoring; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007263:Infusions, Parenteral; D016014:Linear Models; D008297:Male; D008657:Metabolic Clearance Rate; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008954:Models, Biological; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010538:Peritonitis / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology; D011446:Prospective Studies; D011793:Queensland; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D005839:Gentamicins