Drug distribution in dog brain studied by positron emission tomography.
We used positron emission tomography to monitor the distribution of radioactivity in dog brain and muscle following i.v. administration of 11C-labelled antipyrine, imipramine, and quinidine. Twenty-five sequential scans of a transaxial slice of the head were performed within 90 min; radioactivity in plasma was measured in a gamma-counter. Following i.v. injection of [11C]antipyrine (50 mg kg-1; 9-68 mCi; n = 10), the decay of plasma activity was accompanied by rapid uptake in brain and variable uptake in muscle, immediately followed by a redistribution leading to equalization of the radioactivity in the tissues. Administration of [11C]imipramine (4 mg kg-1; 30-110 mCi; n = 8) was followed by a rapid build-up of a sustained gradient between high brain, and low plasma and muscle radioactivity. After i.v. injection of [11C]quinidine (1 mg kg-1; 11-87 mCi; n = 10), radioactivity in brain was low, with higher activity in plasma and muscle throughout the experiment. Positron emission tomography thus revealed for each drug a distinct pattern of distribution consistent with established properties of the compounds. This technique seems promising for the study of early drug distribution, notwithstanding certain limitations.
Agon
P
P
Heymans Institute of Pharmacology, University of Gent, Belgium.
Braeckman
R
R
Van Haver
D
D
Denutte
H
H
Goethals
P
P
Donche
H
H
Vermeullen
F
F
Deman
J
J
Kaufman
J M
JM
D000818:Animals; D000983:Antipyrine / Q000097:blood / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes; D004285:Dogs; D007099:Imipramine / Q000097:blood / Q000493:pharmacokinetics*; D009132:Muscles / Q000000981:diagnostic imaging / Q000378:metabolism; D011802:Quinidine / Q000097:blood / Q000493:pharmacokinetics*; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D011802:Quinidine; D007099:Imipramine; D000983:Antipyrine