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Research Papers

Microdialysis Technique to Quantify Drug Concentration in Human Intervertebral Disks

[+] Author and Article Information
Hyun Kyu Han

Biomechanical Testing Facility, UCSF/SFGH Orthopaedic Trauma Institute, San Francisco, CA

Jenni Buckley1

Biomechanical Testing Facility, UCSF/SFGH Orthopaedic Trauma Institute, San Francisco, CAjennibuckleyphd@gmail.com

Kathy Kursa

 Medtronic Spinal and Biologics, Sunnyvale, CA

Conor O’Neill, Jeffrey Lotz

Department of Orthopaedic Surgery, University of California-San Francisco, San Francisco, CA

1

Present address: Taylor Collaboration, St. Mary's Medical Center, 450 Stanyan Street, San Francisco, CA 94117.

J. Med. Devices 4(4), 041009 (Dec 06, 2010) (4 pages) doi:10.1115/1.4003006 History: Received January 11, 2010; Revised November 08, 2010; Published December 06, 2010; Online December 06, 2010

No dependable method has yet been established to find time-dependent concentrations of substances injected into the intervertebral disk. This study investigated the feasibility of microdialysis in the measurement of local concentrations of a low-molecular weight drug in the human lumbar disk. A quasi-static experiment and a dynamic computer finite element simulation were used to study the spread of lidocaine in the lumbar disk. Fresh-frozen cadaveric lumbar motion segments were immersed in a 0.1% lidocaine HCl solution for 6 days prior to continuous microdialysis sampling for 30 min at the posterolateral annulus. Samples were collected every 10 min, for a total of three samples per probe. To maintain quasi-static conditions, where the output of lidocaine was equal to the diffusion rate, the microdialysis flow rate was set to 0.6μl/min. The finite element model treated the disk as poroelastic tissue under compressive load and introduced 1 ml of 4% lidocaine into the nucleus pulposus. Higher microdialysis flow rates suffered from significant losses during consecutive recoveries. Relative recovery in the annulus at 0.6μl/min was found to be 53.3%±16.2% of the initial solution. This was determined to be a result of low diffusivity of lidocaine through tissue. The FEA model predicted low diffusivity of lidocaine and slow transport to the posterolateral annulus if no fissures were present in the annulus. The results from in vitro experiments and computer simulations showed that while microdialysis can take reliable concentration measurements in the posterolateral annulus, probe placement near a fissure is critical if a measurement is to be made immediately following injection of a drug into the nucleus.

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Figures

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Figure 1

Microdialysis probes inserted into a lumbar disk immersed in 1× PBS at 38°C.

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Figure 2

Flow rate versus relative recovery with varying collection time in 100 ng/ml lidocaine. Error bars show 1 S.D. N=4 for all samples.

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Figure 3

Relative recovery of 1 mg/ml lidocaine in situ, specimen 1. Recovery in the annulus was measured at 2 different flow rates. Error bars represent 1 S.D. in measurement.

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Figure 4

COMSOL simulation of 1 cc lidocaine injected into a healthy intervertebral disk, immediately after injection and 24 h post-injection. Colored regions indicate physiologically effective concentration.

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