DISPOSITION KINETICS OF MOCLOBEMIDE, A NEW MAO-A INHIBITOR, IN SUBJECTS WITH IMPAIRED RENAL-FUNCTION

A single intravenous and oral dose of moclobemide (Ro 11–1163) was administered to 13 subjects with varying degrees of renal impairment (creatinine clearances ranging from 0 to 40 mL/min). The resulting disposition and absorption parameters of moclobemide were more variable than but, with the exception of mean absorption time, were not significantly different from values obtained in another study conducted in 12 normal healthy subjects. There were no relationships between any of the disposition parameters and renal function as measured by creatinine clearance. The disposition of two metabolites of moclobemide were partially characterized from plasma data. One of these (Ro 12–8095) appears to be formation rate‐limited and, from available data, behaves in a manner similar to what has been observed in normals. The other metabolite (Ro 12–5637) has a long apparent disposition half‐life and is present in greater concentrations in the renally impaired compared to the normal subjects. The latter observation may reflect reduced elimination clearance in the renally impaired subjects. Based upon the results of this study there does not appear to be any need to alter the normal dosing regimen of moclobemide in subjects with renal impairment in order to achieve drug concentrations similar to those in healthy subjects. 1990 American College of Clinical Pharmacology