Initial evaluation of low-dose phenobarbital as an indicator of compliance with antimalarial drug treatment.

Poor compliance with antimalarial therapy is often suspected but hard to prove. Findings are reported from efforts to create a model for predicting the plasma concentration of phenobarbital given in low doses together with antimalarial drugs as an indicator of compliance. 50 patients with confirmed falciparum malaria attending Mae Sod Hospital in Thailand were randomized into 5 groups and given malaria therapy together with phenobarbital daily for 3-7 days. Plasma samples with which to determine phenobarbital concentrations were taken just before the daily dose of phenobarbital. Although there was a clear and predictable individual pattern of blood concentrations following each dose of phenobarbital inter-individual variation in blood levels was significant and reduced the predictive value of blood concentrations beyond the second days dose. It is unclear what caused the observed variations. Results for the 5-day artesunate regimen suggest that phenobarbital may be a useful marker of compliance if the patient stops medication after 3 days while for the quinine-tetracycline regimen it may be possible to differentiate subjects when there exists a 3-day difference in treatment. Phenobarbital is a better discriminant when dosing occurs every 24 hours as with artesunate rather than the 8-hourly regimen for quinine-tetracycline.