Motie M, Schaul K W, Potempa L A
Immtech International Inc., Evanston, IL 60201, USA.
Drug Metab Dispos. 1998 Oct;26(10):977-81.
Iodinated forms of C-reactive protein (CRP), soluble modified CRP (mCRP-sol), and suspended mCRP (mCRP-susp) were injected iv into CD-1 mice, for analysis of their pharmacokinetics (PK) and biodistribution (BD). The plasma half-life of 125I-CRP, measured as 4.7 hr, agrees closely with previous reports. The PK and BD characteristics for 125I-mCRP-sol and 125I-mCRP-susp were comparable to each other and were distinctly different from those measured for CRP. Whereas approximately 50% of 125I-CRP was recoverable from plasma 5 min after injection, only approximately 5% of 125I-mCRP was similarly recoverable. The estimated volume of distribution at steady state calculated for either form of 125I-mCRP was approximately 10-fold greater than that calculated for 125I-CRP (23. 4-27.6 and 2.4 ml, respectively). The estimated mean residence times for 125I-mCRP were approximately 2 times longer than that measured for 125I-CRP (9.5-11.5 hr, compared with 4.9 hr). At both 4- and 24-hr time points, substantial amounts of 125I-mCRP were selectively distributed in the bone marrow. At 24 hr, approximately 25% of the injected 125I-mCRP-sol and 125I-mCRP-susp was localized to the bone marrow (corresponding to 92% of injected dose/g of tissue). At this time point, only 8% (or 27%/g) of 125I-CRP was localized to the bone marrow. Overall, the data presented indicate that 1) mCRP has PK and BD characteristics distinct from those of CRP; 2) injected mCRP, although it is rapidly cleared from the general circulation, accesses large body areas and is selectively localized to the bone marrow; and 3) all forms of CRP appear to be excreted in the urine.
将碘标记形式的C反应蛋白（CRP）、可溶性修饰CRP（mCRP-sol）和悬浮mCRP（mCRP-susp）静脉注射到CD-1小鼠体内，以分析它们的药代动力学（PK）和生物分布（BD）。125I-CRP的血浆半衰期测定为4.7小时，与先前的报道非常一致。125I-mCRP-sol和125I-mCRP-susp的PK和BD特征彼此相当，且与CRP的测量结果明显不同。注射后5分钟，约50%的125I-CRP可从血浆中回收，而类似地，只有约5%的125I-mCRP可回收。为两种形式的125I-mCRP计算的稳态分布容积估计值比为125I-CRP计算的值大约10倍（分别为23.4 - 27.6和2.4 ml）。125I-mCRP的估计平均驻留时间比125I-CRP测量的时间长约2倍（分别为9.5 - 11.5小时和4.9小时）。在4小时和24小时时间点，大量的125I-mCRP选择性地分布在骨髓中。在24小时时，注射的125I-mCRP-sol和125I-mCRP-susp中约25%定位于骨髓（相当于每克组织注射剂量的92%）。在这个时间点，只有8%（或每克27%）的125I-CRP定位于骨髓。总体而言，所呈现的数据表明：1）mCRP具有与CRP不同的PK和BD特征；2）注射的mCRP虽然从体循环中迅速清除，但可进入身体的大片区域并选择性地定位于骨髓；3）所有形式的CRP似乎都通过尿液排泄。
