Distribution of radioactivity in bone and related structures following administration of [14C]-dalbavancin to New Zealand White rabbits
Abstract number: p1537
Solon E., Dowell J.W., Lee J., King S.P., Damle B.
Methicillin-resistant Staphylococcus joint infection due to peri-operative contamination is a complication after arthroplasty. The objective of this study was to assess the distribution of radioactivity in bone and related structures using quantitative autoradiography after administration of [14C]-dalbavancin in rabbits.
New Zealand White male rabbits were given a single intravenous (IV) bolus dose of 20 mg/kg [14C]-dalbavancin (n = 18) or control vehicle (n = 3). Plasma, cerebrospinal fluid (CSF), bone, bone marrow, and nucleus pulposus were collected at 12, 24, 72, 120, 168 and 336 h post-dose by necropsy, homogenized, combusted, and analysed for total drug-derived radioactivity using liquid scintillation counting (LSC). In addition, the left hindlimb from 1 rabbit/time point was flash-frozen and cryosectioned for quantitative autoradioluminography.
[14C]-dalbavancin-derived radioactivity was rapidly and widely distributed into bone, bone marrow and, to a lesser extent, in CSF and nucleus pulposus. Autoradioluminography data indicated that concentration of radioactivity was highest in bone marrow, whole blood, articulate cartilage, ligament, epiphyseal plate, periostium, and meniscus. At 336 h post-dose, [14C]-dalbavancin-derived radioactivity was measurable in all tissues, and remained at relatively high concentrations in bone marrow (30.27 mg equiv/g), epiphyseal plate (8.42 mg equiv/g), periostium (5.18 mg equiv/g), and articular cartilage (4.84 mg equiv/g). In homogenized bone using LSC, mean concentration after 336 hours was 1.96 mg equiv/g.
[14C]-dalbavancin-derived radioactivity rapidly penetrated knee joint tissues and persisted at relatively high concentrations for at least 336 h after a single IV dose in rabbits.
|Session name:||XXIst ISTH Congress|
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