RT Journal Article
SR Electronic
T1 Biodistribution and Clearance of<sup>125</sup>I-Labeled C-Reactive Protein and <sup>125</sup>I-Labeled Modified C-Reactive Protein in CD-1 Mice
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 977
OP 981
VO 26
IS 10
A1 Marjan Motie
A1 Katie W. Schaul
A1 Lawrence A. Potempa
YR 1998
UL http://dmd.aspetjournals.org/content/26/10/977.abstract
AB 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 and125I-mCRP-susp were comparable to each other and were distinctly different from those measured for CRP. Whereas ∼50% of 125I-CRP was recoverable from plasma 5 min after injection, only ∼5% of 125I-mCRP was similarly recoverable. The estimated volume of distribution at steady state calculated for either form of125I-mCRP was ∼10-fold greater than that calculated for 125I-CRP (23.4–27.6 and 2.4 ml, respectively). The estimated mean residence times for125I-mCRP were ∼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 of125I-mCRP were selectively distributed in the bone marrow. At 24 hr, ∼25% of the injected125I-mCRP-sol and125I-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. The American Society for Pharmacology and Experimental Therapeutics