Influence of age, frailty and liver function on the pharmacokinetics of brofaromine.
OBJECTIVE
The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66-92 y) and 12 healthy volunteers (20-35 y).


METHODS
Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance).


RESULTS
In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 mumol*h.l-1, clearance was reduced (5.0 vs. 11.8 l.h-1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r = 0.41, P = 0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r = 0.94, P < 0.0001).


CONCLUSIONS
Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.
Zeeh
J
J
Chair of Internal Medicine and Gerontology, University Erlangen-Nürnberg, Germany.
Fuchs
L
L
Bergmann
W
W
Antonin
K H
KH
Degel
F
F
Bieck
P
P
Platt
D
D
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D002110:Caffeine / Q000097:blood; D002849:Chromatography, Gas; D018592:Cross-Over Studies; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D005260:Female; D016330:Frail Elderly; D006207:Half-Life; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010880:Piperidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012044:Regression Analysis; D013012:Sorbitol / Q000097:blood
D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; D002110:Caffeine; D013012:Sorbitol; C038213:brofaromine; D019388:Cytochrome P-450 CYP1A2