A comparison of a short half-life marker (low-dose isoniazid), a long half-life pharmacological indicator (low-dose phenobarbitone) and measurements of a controlled release 'therapeutic drug' (metoprolol, Metoros) in reflecting incomplete compliance by volunteers.
1. Although, long half-life compounds appear to be more appropriate pharmacological indicators of compliance with treatment, short half-life markers or measurements of short half-life therapeutic drugs are frequently used. 2. We have compared the usefulness of low-dose phenobarbitone (a long half-life indicator), low dose isoniazid (a short half-life marker) and controlled release metoprolol (Metros) (a controlled release formulation of a short half-life 'therapeutic' drug) in seven volunteers with simulated partial (two thirds) compliance. 3. Detection of isoniazid metabolites in urine had an 83% sensitivity and 94% specificity for detecting ingestion within the previous 24 h and 100% sensitivity and 82% specificity for detecting ingestion within the past 6 h but gave no indication of the longer term pattern of compliance. 4. At 28 days (a time when steady-state would be obtained for all three drugs) phenobarbitone plasma levels were 70% (66-76%)--median and interquartile range--of the expected steady-state level if compliance had been complete. Corresponding figures for metoprolol were 82% (37-100%). 5. Measurement of phenobarbitone was much superior to isoniazid or metoprolol measurements in reflecting partial compliance over the previous 1 to 4 weeks.
Hardy
E
E
University Department of Medicine, University of Leeds.
Kumar
S
S
Peaker
S
S
Feely
M
M
Pullar
T
T
D000284:Administration, Oral; D000328:Adult; D003692:Delayed-Action Preparations; D005260:Female; D006207:Half-Life; D006801:Humans; D007538:Isoniazid / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D008790:Metoprolol / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D010634:Phenobarbital / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D003692:Delayed-Action Preparations; D008790:Metoprolol; D007538:Isoniazid; D010634:Phenobarbital