1 A ‘low‐dose’ combined oral contraceptive steroid (OCS) preparation containing 30 microgram ethinylo‐estradiol and 150 microgram levonorgestrel was found to reduce significantly antipyrine clearance in a group of women acting as their own controls. 2 An OCS preparation containing only a progestogen (75 microgram norgestrel) did not reduce antipyrine clearance in a second group of women. 3 The evidence suggesting that the oestrogen component of combined OCS preparations could be responsible for the reduction in antipyrine clearance is discussed.

Iproniazid (25–100 mg/kg) produced a marked, dose-related reduction in antipyrine elimination in the rabbit, whereas reductions produced by nitrazepam (32 mg/kg) or SKF 525 A (25 and 40 mg/kg) were small. Phenobarbitone, 10 mg/kg chronically, increased antipyrine elimination. The small inhibitory effect of SKF 525A on antipyrine metabolism in the rabbit was unexpected compared to the marked effect in the rat.

No abstract

1The prolongation of pentobarbitone sleeping times by five benzodiazepines, administered by prior intraperitoneal injection, was measured in mice. The pentobarbitone was injected either intraperitoneally or intracerebroventricularly. For each benzodiazepine, the prolongation was dose-related and differences in potency between benzodiazepines were not marked. 2 The percentage prolongation of sleeping times produced by most of the benzodiazepines was greater when the pentobarbitone was given intracerebroventricularly and was explained by a preferential addition of CNS depressant effects associated with this route. 3 To test whether the action of intraperitoneally administered pentobarbitone had been influenced by a metabolic component, the effects of nitrazepam on drug metabolism, measured by changes in plasma phenazone levels in the mouse, were studied. Nitrazepam (32 mg/kg, i.p.) produced a 23% reduction in the rate of phenazone metabolism. 4 Nitrazepam was also shown to have produced a transient fall in body temperature. Calculations based on Qlo values suggested that this hypothermia accounted, at most, for half the metabolic change measured.

The pharmacokinetics of high-dose rectal metoclopramide have been studied in nine patients after administration of 150-mg suppositories. The results have been compared to the pharmacokinetics of the drug in five patients who received the same dose of metoclopramide intravenously. Administration of a metoclopramide suppository achieved plasma drug concentrations that are associated with the effective treatment of cytotoxic drug-induced nausea and vomiting. In three patients who received the drug by both routes the systemic availability of the suppository appeared to be complete. High-dose metoclopramide suppositories are convenient and may be advantageous in the treatment of medical oncology out-patients.