Pharmacokinetic analysis of blood distribution of intravenously administered 153Gd-labeled Gd(DTPA)2- and 99mTc(DTPA) in rats.
Rat plasma distribution data obtained following IV administration of 99mTc(DTPA) alone or after co-administration of 99mTc(DTPA) and 153Gd-labeled Gd(DTPA)2- at 0.001, 0.1, and 1.0 mmol Gd/kg were evaluated using compartmental modeling techniques. A three-compartment open model was found to fit the data significantly better (P less than 0.01) than a two- or four-compartment open model. This model incorporates and links the plasma and urine data and includes a delay to account for the transit time through the kidneys/ureters. The two nonplasma compartments of the model were assumed to be related to rapidly and slowly equilibrating tissues. Tc(DTPA) and Gd(DTPA)2- had nearly identical pharmacokinetic profiles in plasma and the rate constants were essentially the same. No significant dose dependent pharmacokinetic differences were found for the range of Gd(DTPA)2- doses tested. Simulations of the proposed three-compartment model were used to generate concentration-time curves for each of the three compartments.
Wedeking
P
P
Squibb Institute for Medical Research, New Brunswick, New Jersey 08903.
Eaton
S
S
Covell
D G
DG
Nair
S
S
Tweedle
M F
MF
Eckelman
W C
WC
D000818:Animals; D001810:Blood Volume; D016001:Confidence Intervals; D003287:Contrast Media / Q000008:administration & dosage; D005682:Gadolinium / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine; D019786:Gadolinium DTPA; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological; D009942:Organometallic Compounds / Q000008:administration & dosage; D004369:Pentetic Acid / Q000008:administration & dosage; D011868:Radioisotopes / Q000008:administration & dosage / Q000097:blood* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D016284:Technetium Tc 99m Pentetate / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine; D013997:Time Factors; D014018:Tissue Distribution
D003287:Contrast Media; D009942:Organometallic Compounds; D011868:Radioisotopes; D004369:Pentetic Acid; D005682:Gadolinium; D019786:Gadolinium DTPA; D016284:Technetium Tc 99m Pentetate