Low CL, Bailie GR, Evans A, Eisele G, Venezia RA
Pharmacokinetics of once-daily IP gentamicin in CAPD patients
Perit Dial Int
(Aug) 16:379-384 1996

Once daily intraperitoneal (IP) aminoglycoside (either gentamicin or
tobramycin) is now recommended for treatment of Gram negative peritonitis in
PD patients. The rationale for this approach is that aminoglycosides, since
they display concentration-dependent killing, will achieve better cidal
activity at higher concentrations; at the same time, since antibiotic
otovestibular uptake is a saturable process, less uptake will occur with
once
daily therapy, thus minimizing toxicity. However, there are few data as to
the efficacy of this regimen.
In this study, 10 patients on CAPD (4 daily exchanges) without peritonitis
received a single IP dose of 0.6 mg/kg gentamicin in the first exchange and
blood and dialysate samples were collected at 0, 0.5, 1, 2, 3, 6 (end of
first dwell period) and 24 hrs later. Drug levels were also determined in
the last three spent exchanges. The bioavailability of gentamicin was 56%
over a six-hour dwell period and the half-life was 36 hours. Mean peak
serum
concentrations of gentamicin were 1.37 mg/L at the end of the 6 h dwell and
0.9 mg/L at 24 h. Dialysate antibiotic concentrations were > 10 mg/L at all
times during the first exchange but < 1 mg/L in all subsequent exchanges.
The authors conclude that once daily IP gentamicin may not produce adequate
serum and dialysate antibiotic concnetrations to treat peritonitis.
Comment: This is a well-done pharmacokinetic study; however, it was
performed in patients without peritonitis. In the presence of peritonitis,
uptake of gentamicin into the systemic circulation may have been much
greater, thus altering the results. More importantly, since aminoglycosides
have a post-antibiotic effect, it is not clear as to whether cidal levels
need to be maintained for more than 6 h of each 24 h period. In clinical
practice, treatment with an additional antibiotic (such as oral
ciprofloxacin) in addition to the aminoglycoside will supply an additional
margin of safety. (David J. Leehey, M.D., Loyola University at
Chicago)