A model to evaluate the pharmacokinetic and pharmacodynamic variables of extended-release products using in vivo tissue microdialysis in humans:: Bupivacaine-loaded microcapsules

被引:34
作者
Kopacz, DJ
Bernards, CM
Allen, HW
Landau, C
Nandy, P
Wu, DL
Lacouture, PG
机构
[1] Virginia Mason Clin, Dept Anesthesiol, Seattle, WA 98111 USA
[2] Univ Washington, Seattle, WA 98195 USA
[3] Purdue Pharma LP, Med Res, Stamford, CT USA
[4] Purdue Pharma LP, Clin Pharmacokinet, Stamford, CT USA
[5] Magidom Discovery LLC, Westport, CT USA
[6] Univ Penn, Dept Anesthesia, Philadelphia, PA 19104 USA
关键词
D O I
10.1213/01.ANE.0000067531.49000.C1
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Biodegradable microcapsules produce an ultra-long duration of local anesthesia. We hypothesized that this duration is caused by the sustained-release of bupivacaine from the microcapsules into the surrounding tissue. Previous studies investigated the pharmacokinetics (PKs) of bupivacaine after release from microcapsules and absorption into the systemic circulation. Microdialysis sampling can determine the PKs of any drug at its site of injection. This study was performed to characterize the PKs of bupivacaine and dexamethasone released from microcapsules at a subcutaneous injection site over a 96-h period in volunteers. Bupivacaine concentrations were compared with clinical variables of local anesthetic blockade. This study demonstrates that bupivacaine is released in a sustained manner from microcapsules, that bupivacaine concentrations increase for 24-34 h after microcapsule injection, and that analgesia parallels the tissue bupivacaine concentration obtained by microdialysis. Analgesia was equally rapid in onset with aqueous and microcapsule bupivacaine (P = 0.23). Analgesia was still present at 78% of microcapsule-injected sites after 96 h, significantly longer than for aqueous bupivacaine (P < 0.001). Mild pruritus was the most common side effect, occurring with 56% of the microcapsule injections. Dexamethasone-containing bupivacaine microcapsules are well tolerated and produce a prolonged duration of skin analgesia. Systemic absorption of bupivacaine produces higher peak plasma levels after aqueous injection than after microcapsule injection, despite the injection of a threefold larger load of bupivacaine in the latter.
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页码:124 / 131
页数:8
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