Gentamicin concentrations in human subcutaneous tissue

Abstract

Wound infections frequently originate from the subcutaneous tissue. The effect of gentamicin in subcutaneous tissue has, however, normally been evaluated from concentrations in blood or wound fluid. The aim of the present study was to investigate the pharmacokinetic properties of gentamicin in human subcutaneous adipose tissue by a microdialysis technique. Seven healthy young volunteers each had four microdialysis probes placed in the fat (subcutaneous) layer of the abdominal skin. After the administration of a 240-mg gentamicin intravenous bolus, consecutive measurements of the drug concentrations in serum and subcutaneous interstitial fluid were obtained simultaneously for 6 h. The tissue gentamicin concentration peaked after 10 to 30 min. The peak concentration in the tissue was 6.7 +/- 2.0 mg.liter-1 (standard deviation), equivalent to 39.1% of the peak concentration in serum. The area under the concentration-versus-time curve for the first 6 h in the tissue was 1,281 +/- 390.0) mg.min liter-1, equivalent to 59.7% of the area under the concentration-versus-time curve in serum. It is concluded that the microdialysis technique can be used to make dynamic and quantitative measurements of the gentamicin concentration in human subcutaneous tissue. In this adipose tissue, the peak concentrations of gentamicin were approximately seven times the MIC for Pseudomonas aeruginosa and 33 times the MIC for Staphylococcus aureus after the administration of an intravenous bolus of 240 mg, indicating the presence of sufficient concentrations in the adipose tissue to be effective against common bacteria.

Class-dependent relevance of tissue distribution in the interpretation of anti-infective pharmacokinetic/pharmacodynamic indices

“…For example, in subcutaneous adipose tissue gentamicin had C max and AUC 0-360 values that were ca. 39% and 60% of the values determined from plasma, respectively [46]. Even when protein binding is considered (ca.…”

In vivo pharmacokinetics of a gentamicin-loaded collagen sponge in acute periprosthetic infection: Serum values in 19 patients

“…The peak concentrations measured in the serum gave peak/MIC ratios of 3.5:1 to 8:1 for P. aeruginosa (MIC 0.9 mg/L), 16:1 to 36:1 for S. aureus (MIC 0.2 mg/L) and 2.3:1 to 5.1:1 for Klebsiella spp. (MIC 1.4 mg/L), which are representative values for members of the Enterobacteriaceae family (Lorentzen et al 1996). Apart from 2 patients with reduced clearances (cases 17 and 19 in Table 1), all patients had renal clearances within the normal range.…”

Evaluation of in vitro synergy between vertilmicin and ceftazidime against Pseudomonas aeruginosa using a semi-mechanistic pharmacokinetic/pharmacodynamic model

“…The dosing regimen used in the study was 1 mg/kg once daily for vertilmicin and 0.5 g three times daily (initial concentration 45 mg/L) for ceftazidime, given as an i.v. bolus according to the clinical dosing and unbound fraction information of gentamicin [16][17][18] and ceftazidime [23,24]. The simulation was performed 1000 times with mean values plotted as lines and 95% CIs plotted as shaded bands.…”

“…5 × 10 5 CFU/mL and were then incubated at 37 • C for 2 h before adding antibiotics. The initial concentration of vertilmicin in flasks was set to 20 mg/L, equivalent to a 5 mg/kg single dose, based on the clinical dose and unbound fraction information of gentamicin, since the same information is unavailable for vertilmicin [16][17][18]. Afterwards, all of the flasks were incubated at 37 • C for up to 24 h. In every 1 h, 4.4 mL of antibiotic-containing medium was taken from each flask by a syringe and the same volume of sterile antibioticfree broth was injected to mimic elimination of the drug in the human body according to the reported half-life of ca.…”

“…bolus according to the clinical dosing of gentamicin [16][17][18]. The simulation was performed 1000 times with mean values plotted as lines and 95% CIs plotted as shaded bands.…”