Gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid interaction with clinical drugs in rats.
OBJECTIVE
To investigate whether the hepatic enhancement characteristics of Gd-EOB-DTPA are influenced by the preapplication of a variety of commonly used clinical pharmaceuticals (eg, antibiotics, antineoplastic drugs, corticosteroids, antiarrhythmia drugs, antianxiety drugs, scopolamine, and xanthine derivatives).


METHODS
Eleven commercially available drugs (prednisolone, rifampicin, doxorubicin hydrochloride, cisplatin, propranolol hydrochloride, scopolamine butylbromide, theophylline, ampicillin, cefotaxime sodium, verapamil hydrochloride, and diazepam) were intravenously (IV) injected in rats at three to five times the clinical dose (n = 3 or 6 per drug). A control group of rats was given saline (n = 6). Gd-EOB-DTPA (25 micromol Gd/kg IV) was administered to rats 30 minutes after the injections of the clinical drugs. Liver MR imaging was performed with a 2.0 T animal imager before and up to 60 minutes after injection. Enhancement (ENH) (%) and area under the data from time versus enhancement curve (AUD) were calculated. RESULTS Rifampicin was the only drug that significantly decreased the hepatic enhancement by Gd-EOB-DTPA. Both the maximum enhancement of the liver and the AUD were significantly reduced when rifampicin was preinjected. Preinjection of prednisolone, doxorubicin hydrochloride, cisplatin or propranolol hydrochloride yielded a slightly but significant increased maximum enhancement of the liver. Furthermore, the enhancement declined more slowly when these drugs were preadministered, yielding a large AUD. None of the other drugs showed a significant effect on hepatic enhancement.


CONCLUSIONS
Rifampicin exerted a clinically significant decrease on hepatic enhancement by Gd-EOB-DTPA. Prednisolone, doxorubicin hydrochloride, cisplatin, or propranolol hydrochloride slightly but significantly increased the hepatic enhancement by Gd-EOB-DTPA.
Kato
Naoki
N
Preclinical Development Department, Nihon Schering K.K., Osaka, Japan. nkatoh@schering.co.jp
Yokawa
Takashi
T
Tamura
Ayako
A
Heshiki
Atsuko
A
Ebert
Wolfgang
W
Weinmann
Hanns-Joachim
HJ
D000818:Animals; D019540:Area Under Curve; D003287:Contrast Media / Q000493:pharmacokinetics / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics / Q000494:pharmacology*; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D003287:Contrast Media; C073590:gadolinium ethoxybenzyl DTPA; D019786:Gadolinium DTPA