1. Milk and plasma metronidazole and hydroxymetronidazole concentrations were measured in 12 breast‐feeding patients following multiple doses of metronidazole (400 mg three times daily). All patients received metronidazole in combination with other broad spectrum antibiotics. 2. Plasma concentrations of both parent drug and metabolite were measured in seven suckling infants. Thirty‐five infants were monitored for adverse reactions to maternal metronidazole therapy and two further groups of suckling infants, those whose mothers received either ampicillin alone or no drug therapy, were recruited as controls. 3. The mean milk to plasma ratio (M/P) was 0.9 for metronidazole and 0.76 for hydroxymetronidazole while the mean milk metronidazole concentrations (around Cmax) were 15.5 micrograms ml‐1. The mean milk hydroxymetronidazole concentration was 5.7 micrograms ml‐ 1. 4. Infant plasma metronidazole concentrations ranged from 1.27 micrograms ml‐1 to 2.41 micrograms ml‐1, and the corresponding hydroxymetronidazole concentrations from 1.1 to 2.4 micrograms ml‐1. 5. There were no significant increases in adverse effects in infants which could be attributable to maternal metronidazole therapy. 6. Metronidazole was excreted in milk at concentrations which caused no serious reactions in the infants studied. The drug may therefore be administered at doses of 400 mg three times daily to mothers wishing to breast‐feed their infants.

In an inpatient survey the medication records of 2004 mothers both breast and bottle feeding were examined and the drugs taken in the early postnatal period recorded. No notable differences existed between the types of drugs prescribed for breast feeding and bottle feeding mothers. Iron, vitamins, and mild analgesics were taken routinely by the population, and antibiotics, laxatives, and hypnotics were frequently prescribed. A wide range of other drugs and preparations were taken or used. Although data were available for some of the drugs, there were many whose concentrations in breast milk and potential risk to the suckling infant were unknown.Data are urgently required on hypnotics, narcotic analgesics, antiemetics, antihistaminics, and some antimicrobial agents with respect to their concentrations in breast milk and their safety for the suckling infant. Introduction During the past decade there has been a considerable increase in the number of mothers breast feeding their newborn; for example, a study in Harrow found an increase from 38% in 1972 to 69% in

Objective-To see whether changes in prescribing of oral antibacterials in Northern Ireland show the need for a community antibiotics policy.

Because of the introduction of indicative drug budgets in the UK and their likely association with prescribing from a drug formulary, we have studied the effect of the introduction without continued reinforcement of a voluntary practice formulary on antimicrobial prescribing in a group practice. Detailed prescribing feedback for two matched periods before and after the launch of the Northern Ireland Faculty of the Royal College of General Practitioners practice formulary was compared. The parameters chosen were adherence to the formulary, generic prescribing and costs. A slight increase in prescriptions dispensed (3.5%) was observed between the two periods but prescribing costs increased by 32%. There was a 5.9% fall in the number of prescriptions for formulary agents following the launch of the formulary and a major increase (60%; P < 0.01) in the use of non-formulary antimicrobials particularly penicillins and tetracyclines. It was concluded that the high level of formulary prescribing prevalent during the production of the formulary was not maintained following its launch probably because of the lack of reinforcement.

JOURNAL OF THE BRITISH MENOPAUSE SOCIETY, Supplement S3, zoor metabolism. The oral contraceptive containing ethinylestradiol and the progestin norethisterone acetate did not elicit a higher D-ring metabolism, which is considered to increase breast cancer risk. For the oral contraceptive containing dienogest a significant decrease of the ratio in favour of the antiestrogenic oestradiol metabolite was observed. Introduction. Oestrogen replacement therapy is well established for treating the systemic (vasomotor) and local (urogenital atrophy) symptoms associated with the menopause. Previously, intravaginal oestradiol (E z) administration was only able to treat local symptoms, while oral or transdermal products were required to provide sufficient quantities of E z to treat systemic and local symptoms. An intravaginal ring (IVR) using the E z prodrug, oestradiol acetate (EA), was developed to provide sufficient E z to treat both local and systemic symptoms. Methods. Three studies were conducted to characterise the pharmacokinetics of E z and oestrone (E l ) following administration of EA-IVR single-doses to healthy postmenopausal women. In Study 1, EA-IVRs providing nominal doses of 50 mg and 75 mg for 14 days and 100 mg Ez/day for 12 weeks were administered to 12 subjects according to an escalating-dose design. In Study 2, EAIVRs providing 100 mg~/day were administered to 12 subjects for three days. In Study 3, EA-IVRs providing 50 mg~/day were administered to 26 subjects for 13 weeks. Serum~and E I concentrations were determined by enzyme-linked fluorescent assay or GCIMS methods. Results. The E z concentration-time profile was characterised by rapid~absorption (mean tmax <1 h) followed by a short E z distribution phase (rapidly decreasing serum E z concentrations) followed by relatively constant serum E z concentrations to the end of the 12-13 week dosing interval. Average serum E z concentration (Cavg) values following 50 mg, 75 mg, and 100 mg Ez/day for 14 days were 172.5, 201.5 and 292.9 pmol/L, respectively. Cavg values after 12-13 weeks treatment were 149.7 (50 mg Ez/day) and 280.4 pmollL (100 mg Ez/day). Serum E] concentrations were similar to but generally lower those for E z. The EA-IVR was generally well tolerated. Conclusions. Average serum E z concentrations following single-dose EA-IVR administration (approximately 150-280 pmollL) are likely to be effective in treating both the systemic and local symptoms of oestrogen deficiency.