Pharmacokinetics and stability of caldiamide sodium in rats.
Gadodiamide (CAS 122795-43-1) injection (Omniscan) is a formulation composed of gadolinium (III) complexed with diethylenetriaminepentaacetic acid bis-methylamide (Gd DTPA-BMA) and the sodium calcium complex of the same ligand, known as caldiamide sodium (CAS 122760-91-2, NaCa DTPA-BMA), in a molar ratio of 20:1. Following intravenous dosing of NaCa DTPA-BMA (0.015 mmol/kg) in a 14C-labeled form, plasma concentrations of the drug declined rapidly with an elimination half-live of 0.31 h, a distribution volume of 244 ml/kg and a plasma clearance of 9.2 ml/min/kg. These results demonstrate that NaCa DTPA-BMA distributes into the extracellular fluid compartment and is renally excreted via glomerular filtration. Of the dose of radioactivity given, 86.6% was excreted in urine by 4 h after injection, and 95.3% in urine and 3.3% in feces by 120 h. In addition, experiments were done to clarify the in vivo metabolism of NaCa DTPA-BMA. Results show small quantities of transchelatd forms of NaCa DTPA-BMA in urine. HPLC analysis demonstrated these metabolites were the Zn and Cu forms of the drug, resulting from displacement of the Ca ion in the NaCa DTPA-BMA molecule by endogeneous Zn or Cu. Further analyses by HPLC and ICP-AES demonstrate that the unchanged parent drug, the Zn and the Cu forms occur in relative quantities of approximately 92%, 7%, and 1%, respectively. This demonstrates that the Ca ion in caldiamide sodium can be replaced by Zn or Cu ions in vivo, but only to a small extent.
Okazaki
O
O
Developmental Research Laboratories, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Kurata
T
T
Yoshioka
N
N
Hakusui
H
H
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics*; D004355:Drug Stability; D005243:Feces / Q000737:chemistry; D019786:Gadolinium DTPA; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D009942:Organometallic Compounds / Q000737:chemistry* / Q000493:pharmacokinetics*; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013054:Spectrophotometry, Atomic
D003287:Contrast Media; D009942:Organometallic Compounds; D004369:Pentetic Acid; C064925:gadodiamide; D019786:Gadolinium DTPA