MIXED LINEAR AND NONLINEAR DISPOSITION OF LAZABEMIDE, A REVERSIBLE AND SELECTIVE INHIBITOR OF MONOAMINE-OXIDASE-B

1 Single oral doses (100-300 mg) and multiple oral doses (100-350 mg 12 hourly for 7 days) of lazabemide were administered to 35 young and 40 elderly healthy subjects. Plasma concentrations of unchanged drug were determined to study the dose-concentration relationship. 2 The elimination phase time course of lazabemide concentrations indicated concentration-dependent elimination after both single and multiple dosing. Nevertheless, maximum concentrations and areas under concentration-time curves increased almost proportionally with dose and accumulation after chronic dosing was less than a factor of 2; steady-state concentrations were achieved by the third day of dosing. The apparent half-life determining accumulation was approximately 8-9 h. 3 Drug absorption commenced rapidly after a dose; two components to the absorption process were dectable in young subjects possibly due to simultaneous administration of multiple tablets at the higher doses. 4 Observations after single and multiple dosing were described with a compartmental model allowing for parallel saturable (population mean +/- s.d.: maximum elimination rate V-max/F: 2.8 +/- 1.4 mg h(-1); concentration at half-maximum elimination K-m: 36 +/- 19 mu g 1(-1)) and first-order (CL/F 16 +/- 3.8 1 h(-1)) elimination pathways. No important difference between the young and the elderly subjects was noted in absorption or disposition parameters of lazabemide.