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.

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The bio-availability of betamethasone-17-valerate (Betnovate ointment) in emulsifying ointment (1 in 4 dilution) was investigated in ten subjects using a single-application vasoconstrictor assay; the blanching induced was measured using a skin reflectance spectrophotometer. The vasoconstrictor activity of the diluted preparations decreased with age. There was no significant difference between the vasoconstrictor activity of freshly made Betnovate 1 in 4 in emulsifying ointment and undiluted Betnovate ointment, and between 3-4 week old diluted Betnovate and emulsifying ointment base. Blanching induced by freshly prepared 4, 8 and 16-fold dilutions was not significantly different but a large reduction in blanching occurred on diluting 32-fold with emulsifying ointment. The degradation of betamethasone -17-valerate in emulsifying ointment was quantified by high performance liquid chromatography. More than 60% of the betamethasone -17-valerate underwent degradation within 6 h. There was a simultaneous increase in the concentration of betamethasone-21-valerate which peaked within 2 days and was followed by a slow degradation (half-life 8 days) to betamethasone free alcohol.

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The in vitro dissolution rates of 5 and 10 mg nifedipine capsules from eight suppliers were measured in simulated gastric fluid using the rotating paddle apparatus. A total of fourteen products were tested and the performance was found to be satisfactory for all products (> 80% dissolution in 20 min).

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.

A study was carried out using high performance liquid chromatography (HPLC) to determine the chemical stability of amoxycillin and potassium clavulanate in 250/62 co-amoxyclav oral suspension (Augmentin), stored at room temperature (RT, 20 degrees C) and 8 degrees C over a period of 11 days. The suspension was judged to be acceptable if its components maintained at least 90% of their label concentrations. During the test period, the amoxycillin component was found to be more stable than the clavulanate. Amoxycillin was stable for 7 days at both temperatures. Potassium clavulanate maintained at least 90% of its initial concentration for 7 days at 8 degrees C but showed more than 40% degradation in the same time period at RT. For potassium clavulate the shelf-life, or time taken for the original concentration to drop to 90% of its value (t90) at RT was found to be 2 days.