PHARMACOKINETICS OF GENTACOLL INVESTIGATED BY IN VIVO MICRODIALYSIS. AN EXPERIMENTAL STUDY

Abstract

Objectives: Antimicrobial agents exert their effect inside the interstitial space, which is the site of many infections. Recently, microdialysis was applied to cortical and cancellous bone for the evaluation of gentamicin. The principle of microdialysis is to introduce a semipermeable membrane into bone and perfuse it with liquid, thus enabling dynamic measurements to be made.

The aim of this investigation was to measure pharmacokinetics of a Gentacoll sponge in bone tissue by microdialysis.

Materials and Methods: Nine pigs were randomized to either wet or dry application of a Gentacoll sponge (10cm* 10cm) into the bone marrow of tibia. Two catheters were inserted into cancellous bone tissue, one 1 cm (MD_1cm) and one 2 cm (MD_2cm) apart from the aimed location of the sponge. Then, the Gentacoll sponge was implanted. Wet application was defined as; the sponge was wetted in 2 mL. blood. Dry application was defined as usual surgical procedure. Concentrations of gentamicin were measured in serum and microdialysates on an Abbott Drug Analyser. Data presented are median (range). A rank sum test was performed for statistical analysis. A p-value below 0,05 was considered significant..AUC describes the total amount of gentamicin that passed though the tissue.

Results: The AUC_{6h, serum wet} was 92 (72–129) and AUC_{6h, serum dry} was 196 (142–626) mg*minute/L (P=0.02). The C_{peak, wet-group} was 120 mg/L (33–585) and C_{peak, dry-group} 178 mg/L(59–1294), (P=0.31). The overall (n=9) AUC_MD1cm was 24431 mg*minute/L (5.155–152.855) and similar the AUC_MD2cm 13759 mg*minute/L (6.351–74.573) (P=0,25). The C_{peak, MD 1cm} was 106 (41–354) (P=0.21). was 209 (33–1294) and C_{peak, MD 2cm}

Conclusions: This first study applied microdialysis for pharmacokinetic measurements of a local implant. The distribution of local applied antibiotics into bone tissue is difficult to measure. The small sample size precludes a detailed analysis, but previous found variation on the distribution of gentamicin from a Gentacoll sponge is reproduced in this work. It seems that neither application nor distance had impact on the initial pharmacokinetic of Gentacoll in bone tissue.