1 To assess the potential value of low-dose phenobarbitone (PB) as a marker of compliance we studied the relationship between plasma level of PB and dose (2-16 mg daily) following 3 or 4 weeks treatment in healthy volunteers (n = 26) and in-patient volunteers (n = 7). 2 Also, to simulate poor compliance, PB levels were measured in some volunteers following alternate-day (n = 6) or short-term (n = 5) treatment with similar doses. These levels, expressed as the level: dose ratios (LDRs), did not overlap with those obtained following 3 or 4 weeks of daily PB intake. 3 To evaluate the efficacy of this marker in patients taking other drugs we gave a group of out-patients (n = 24) compound tablets containing B vitamins and a small dose (16 mg) of PB; their compliance over 2-5 weeks was assessed both by measuring plasma levels of PB and residual tablet counting. 4 In the latter study, as well as providing absolute evidence of good compliance by many patients, the plasma levels of PB proved particularly valuable when non-compliant individuals 'forgot' to bring their residual tablets. 5 We suggest that phenobarbitone, in doses low enough to be non-sedative and nonenzyme inducing, is potentially useful as a pharmacological indicator of compliance with drug therapy.

The effects of low‐dose phenobarbitone on three indices of hepatic enzyme induction were studied. Eight healthy volunteers took phenobarbitone 7.5 mg daily for 4 weeks followed by 15 mg daily for 4 weeks; five subjects took 30 mg daily for a further 2 weeks. Phenobarbitone 15 mg daily produced a significant rise in antipyrine clearance (P less than 0.05). Phenobarbitone 30 mg daily produced a further rise, but probably because of the reduced numbers of subjects, this did not achieve significance (P = 0.06). Urinary 6‐beta‐ hydroxycortisol and D‐glucaric acid levels did not change significantly and remained within the range seen in subjects not taking enzyme‐ inducing drugs. We conclude that phenobarbitone 7.5 mg daily produces little (if any) enzyme induction whereas 15 mg, or more, may have the potential to produce drug interactions through enzyme induction.

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