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). CONCLUSION: Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromineclearance.
RCT Entities:
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). CONCLUSION:Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.
Authors: D S Robinson; A Nies; J N Davis; W E Bunney; J M Davis; R W Colburn; H R Bourne; D M Shaw; A J Coppen Journal: Lancet Date: 1972-02-05 Impact factor: 79.321
Authors: P R Bieck; L Firkusny; C Schick; K H Antonin; E Nilsson; R Schulz; M Schwenk; H Wollmann Journal: Clin Pharmacol Ther Date: 1989-03 Impact factor: 6.875
Authors: Claire Johnston; Sarah N Hilmer; Andrew J McLachlan; Slade T Matthews; Peter R Carroll; Carl M Kirkpatrick Journal: Eur J Clin Pharmacol Date: 2014-02-14 Impact factor: 2.953