Richard Brigitte M, Rickert Douglas E, Doolittle Dannette, Mize Amy, Liu Jason, Lawson Charles F
Clinical Research & Drug Safety Assessment, Pacira Pharmaceuticals Inc., San Diego, CA 92121, USA.
ISRN Pharm. 2011;2011:582351. doi: 10.5402/2011/582351. Epub 2011 Dec 27.
We explored the potential for EXPAREL to interact with lidocaine. Sixty (60) male Yucatan Swine were randomized into 20 groups (N = 3/group). EXPAREL (2 or 4 mg/kg) and/or lidocaine HCl solution 1% or 2% (with epinephrine 1 : 200,000) were injected subcutaneously along a 5 cm virtual incision line. The effects on the pharmacokinetics of bupivacaine and lidocaine were examined when 5, 10, 20, and 40 minutes had passed between administration of lidocaine and EXPAREL. Systemic exposure to lidocaine was increased (AUC(0-24 hr) by 48%; C(max) by 1,640%) when lidocaine (4 mg/kg) was followed 5 minutes later by EXPAREL (4 mg/kg) compared to lidocaine administered alone. Plasma bupivacaine was increased (AUC(0-24 hr) by 50-95%; C(max) by 67-1,000%) when lidocaine (4 mg/kg) was followed 5 or 10 minutes later by EXPAREL (4 mg/kg) compared to EXPAREL alone. While EXPAREL should not be admixed with lidocaine, this study shows that local administration of EXPAREL after at least 20 minutes following local administration of lidocaine did not increase the release of either drug.
我们研究了EXPAREL与利多卡因相互作用的可能性。60只雄性尤卡坦猪被随机分为20组（每组N = 3）。将EXPAREL（2或4mg/kg）和/或1%或2%的盐酸利多卡因溶液（含1∶200,000肾上腺素）沿一条5cm的虚拟切口线皮下注射。在利多卡因和EXPAREL给药间隔5、10、20和40分钟时，检测其对布比卡因和利多卡因药代动力学的影响。与单独给予利多卡因相比，利多卡因（4mg/kg）给药5分钟后再给予EXPAREL（4mg/kg）时，利多卡因的全身暴露增加（AUC(0 - 24小时)增加48%；C(max)增加1640%）。与单独给予EXPAREL相比，利多卡因（4mg/kg）给药5或10分钟后再给予EXPAREL（4mg/kg）时，血浆布比卡因增加（AUC(0 - 24小时)增加50 - 95%；C(max)增加67 - 1000%）。虽然EXPAREL不应与利多卡因混合使用，但本研究表明，在局部给予利多卡因至少20分钟后局部给予EXPAREL不会增加两种药物的释放。
