Noninvasive in vivo 13C-NMR spectroscopy in the rat to study the pharmacokinetics of 13C-labeled xenobiotics.
Noninvasive NMR methodology has been developed to enable monitoring of 13C-labeled xenobiotics in the rat in vivo. 2,2-Dichloro-1-(2-chlorophenyl)-1-(4-chlorophenyl)-[3-13C]-propane can be detected in the liver of intact rats by in vivo 13C surface coil NMR spectroscopy after ip administration of the compound. The experiments were performed at 1.9 and 9.4 Tesla. The intrahepatic changes of the signal intensity of the labeled compound were followed as a function of time. In the days following administration, the concentration decreased and dropped to values below the detection limit after 12 days. The study demonstrates the feasibility of studies on pharmacokinetics of 13C-labeled compounds in the rat using noninvasive, in vivo surface coil NMR spectroscopy in animals. The sensitivity allows the detection of a single dose of the drug of 200 mg/kg, but can be improved.
Division of Toxicology, University of Leiden, The Netherlands.
H J
HJ
Muller
D
D
Lanens
T J
TJ
de Cock Buning
F L
FL
van de Vyver
F C
FC
Alderweireldt
R
R
Dommisse
M
M
Spanoghe
G J
GJ
Mulder
J
J
Lugtenburg
D000818:Animals; D002247:Carbon Isotopes; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008939:Mitotane / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D015262:Xenobiotics / Q000493:pharmacokinetics*
D002247:Carbon Isotopes; D015262:Xenobiotics; D008939:Mitotane; C051076:mitometh