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 live r function tests were performed to show whether brofaromine eliminatio n in the elderly could be predicted from noninvasive assessment of CYP 1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clear ance). Results: In the elderly the AUC of brofaromine was significantl y increased (e.g. for the 75 mg dose 43.2 vs 19.9 mu molh . 1(-1), cl earance was reduced (5.0 vs. 11.8 1 . h(-1)), the volume of distributi on was smaller (130 vs. 2301), and the half-life was slightly increase d (19.0 vs. 14.2 h). No significant correlation was observed between h epatic plasma flow and brofaromine clearance (r = 0.41, P = 0.05), whe reas CYP1A2 activity and brofaromine clearance were tightly correlated (r = 0.94, P < 0.0001). Conclusion: Caffeine clearance, a simple, non invasive test of CYP1A2 activity, is predictive of brofaromine clearan ce.