Pharmacokinetics of 70-kilodalton fluorescein-dextran in experimental diabetes mellitus

R Mehvar and JM Reynolds

College of Pharmacy and Health Sciences, Drake University, Des Moines, Iowa.

The pharmacokinetics of fluorescein-labeled dextran with a MW of 70,000 (FD-70) were studied after i.v. injection of single 5-mg/kg doses to control (C), untreated diabetic (D) and insulin-treated diabetic rats. Concentrations of FD-70 in serum, urine and various tissues were determined using a size exclusion chromatographic method. Untreated diabetes caused a striking change in the elimination parameters of FD- 70, whereas the distribution parameters were mostly unaffected by the disease. The area under the serum concentration-time curve (microgram- hr/ml) in D rats (1360 +/- 506) was approximately 8 times that in C rats (175 +/- 16). Consistent with this, the terminal harmonic half- lives of FD-70 in D and C rats were 16.1 and 1.80 hr, respectively. Although the renal clearance of the macromolecule was similar in the two groups, the differences in the area under the serum concentration- time curve values could be accounted for by the substantially lower nonrenal clearance of FD-70 in D rats (0.0297 +/- 0.0296 vs. 0.434 +/- 0.050 ml/min/kg). At 12 hr after the administration of FD-70, concentrations of the macromolecule in the heart, lung, brain and kidneys were negligible. However, the C and D livers contained 53.3 +/- 11.2 and 14.0 +/- 6.8% of the administered dose at this time. Most of the diabetes effects on the disposition of FD-70 were reversed by chronic insulin treatment. It is concluded that the significant differences between D and C rats in their serum concentration-time profiles of FD-70 are likely due to differences in their liver accumulation of the macromolecule.

Volume 264, Issue 2, pp. 662-669, 02/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				B. R. Line, A. Mitra, A. Nan, and H. Ghandehari Targeting Tumor Angiogenesis: Comparison of Peptide and Polymer-Peptide Conjugates J. Nucl. Med., September 1, 2005; 46(9): 1552 - 1560. [Abstract] [Full Text] [PDF]