Summary1. The effects of bretylium have been investigated on the content and subcellular distribution of noradrenaline in cat spleen and on the overflow of noradrenaline in response to stimulation of the splenic nerve. 2. Bretylium, 15 min after its administration, produces a significant depletion of noradrenaline in only the supernatant fraction of an homogenate; at this time adrenergic neurone blockade is evident. This depletion of noradrenaline is apparent up to 18 h later but has disappeared 7 days after the administration of bretylium when nerve function is also restored. ' 3. Both the development of the neurone blockade and the depletion of noradrenaline are prevented by previous administration of ( +)-amphetamine. 4. In bretylium-pretreated cats the noradrenaline content of the supernatant fraction is replenished and the neurone blockade is abolished after treatment with (+)-amphetamine. 5. The depletion of noradrenaline, which is evident 30 min, 60 min and 18 h after treatment with bretylium, from other subcellular fractions-especially the high-speed particulate fraction appears to be unassociated with adrenergic neurone blockade.6. It is concluded that bretylium produces its adrenergic neurone-blocking activity by depleting noradrenaline from a " store " whose amine appears in the supernatant fraction after homogenization. Whilst bretylium is present this "store " cannot refill with noradrenaline.

Seizures are a common cause of neurologic disease, and phenobarbital (PB) is the most commonly used antiepileptic drug. Chronic oral dosing can be challenging for cat owners, leading to poor compliance. The purpose of this study was to determine if the transdermal administration of PB could achieve serum PB concentrations of between 15 and 45 μg/ml in healthy cats. Nineteen healthy cats were enrolled in three groups. Transdermal PB in pluronic lecithin organogel (PLO) was applied to the pinnae for 14 days at a dosage of 3 mg/kg q12h in group 1 (n = 6 cats) and 9 mg/kg q12h in group 2 (n = 7 cats). Transdermal PB in Lipoderm Activemax was similarly applied at 9 mg/kg q12h for 14 days in group 3 (n = 6 cats). Steady-state serum PB concentrations were measured at trough, and at 2, 4 and 6 h after the morning dose on day 15. In group 1, median concentrations ranged from 6.0-7.5 μg/ml throughout the day (observed range 0-11 μg/ml). Group 2 median concentrations were 26.0 μg/ml (observed range 18.0-37.0 μg/ml). For group 3, median concentrations ranged from 15.0-17.0 μg/ml throughout the day (range 5-29 μg/ml). Side effects were mild. One cat was withdrawn from group 2 owing to ataxia and sedation. These results show therapeutic serum PB concentrations can be achieved in cats following chronic transdermal administration of PB in PLO at a dosage of 9 mg/kg q12h. More individual variation was noted using Lipoderm Activemax. Transdermal administration may be an alternative for cats that are difficult to medicate orally.

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Objectives The aim of this study was to compare serum phenobarbital concentrations, adverse events and client satisfaction during 14 weeks of transdermal vs oral phenobarbital administration to epileptic cats. Methods This was a prospective, fixed-order, crossover pilot study. Nine client-owned cats with presumptive or diagnosed idiopathic epilepsy were enrolled. Oral phenobarbital (PO-PB) was administered for weeks 1–14 (median starting dosage of 3.8 mg/kg [2.0–5.4 mg/kg/day] q12h); transdermal phenobarbital (TD-PB) was administered for weeks 14–28 (median starting dosage 18.8 mg/kg/day [17.6–24.0 mg/kg/day] q12h). Serum phenobarbital concentrations (S-PB) were measured at weeks 2, 14, 16 and 28. Client satisfaction questionnaires and biochemistry were evaluated at 14 and 28 weeks. Results Median S-PB concentrations during oral administration were 21 µg/ml (observed range 11–40 µg/ml) at week 2 and 22 µg/ml (8–35 µg/ml) at week 14, and at the higher TD dosage were 18 µg/ml (0–42 µg/ml) at week 16 and 17 µg/ml (7–50 µg/ml) at week 28. Phenobarbital concentrations were significantly correlated with PO dosage at week 2 ( r = 0.75, P = 0.03) but not at weeks 16 and 28. Significantly more dose adjustments were needed during the TD phase ( P = 0.03), but 6/9 owners (67%) still preferred TD to PO administration. Adverse effects were mild and comparable in both groups. Conclusions and relevance Therapeutic S-PB concentrations were achievable in some cats using TD-PB at 18 mg/kg/day q12h. Poor correlation between TD dosage and S-PB concentrations was observed and more dosage adjustments were required during TD administration. These findings necessitate close therapeutic drug monitoring if TD-PB is prescribed.

A time-series prospective study of patients admitted to the hospital for treatment of community-acquired pneumonia was undertaken to determine vancomycin-resistant enterococcal perianal colonization rates among patients who received ceftriaxone with or without erythromycin versus those who received levofloxacin. A colonization rate of 16% (8/51) was found in the ceftriaxone-erythromycin group versus 0% (0/52) in the levofloxacin group .