Potential of concentration monitoring data for a short half-life drug: analysis of pharmacokinetic variability for moclobemide.
The pharmacokinetic variability of moclobemide, a new short half-life reversible selective inhibitor of monoamine oxidase (MAO) was investigated through analysis of concentrations measured during early open clinical use. Eighty-nine depressed patients, aged 21-96 years, were included in the present study. Doses ranged from 200 to 900 mg/day, and the time interval between blood sampling and last drug intake on the previous day was between 8 and 23 h. Intraindividual variability was generally moderate, with a few patients displaying consistently high concentrations despite moderate doses. Interindividual variability for measured concentrations was approximately 300-fold. After concentration decrease with time was taken into account (average half-life estimate of 4.6 h), age was identified as a major factor responsible for between-patient variability. Average concentration increase per decade of age was 38%. Neither gender, weight, height, smoking, nor alcohol intake explained a significant additional part of the variance. Analysis of residuals also suggested that phenytoin co-medication may induce moclobemide metabolism. The present study indicates that concentration monitoring of a newly marketed drug can contribute to gaining insight into its pharmacokinetic behavior and to enhancing its rational use in clinical practice.
Gex-Fabry
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Clinical Research Unit, University Psychiatric Institutions, Geneva, Switzerland.
Balant-Gorgia
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D001549:Benzamides / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002849:Chromatography, Gas; D003866:Depressive Disorder / Q000188:drug therapy; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D020912:Moclobemide; D008996:Monoamine Oxidase Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010672:Phenytoin / Q000493:pharmacokinetics
D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D010672:Phenytoin; D020912:Moclobemide