1 In eight normotensive male volunteers indomethacin decreased both the peak urine flow rate and total sodium excreted within 1 h of an intravenous dose of frusemide.2 Resting effective renal plasma flow and glomerular filtration rate were unchanged by indomethacin, but the increase in both parameters after frusemide was inhibited.3 The early increase in plasma renin activity after frusemide was inhibited by indomethacin. 4 Indomethacin decreased urinary excretion of PGE by 80% and the increase after frusemide was abolished. 5 The urinary excretion of a metabolite of systemic PGI2was unaltered in the 40-60 min period following frusemide.6 The early haemodynamic effects of frusemide are likely to be prostaglandin mediated, but there was no evidence of any change in systemic PGI2 synthesis after frusemide.

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Six patients with end-stage chronic renal failure undergoing haemodialysis were given ofloxacin (600 mg) orally and blood samples were taken at intervals up to 32 h. In four patients samples were also taken before and after haemodialysis. Serum concentrations of ofloxacin, desmethyl ofloxacin and ofloxacin N-oxide were measured by HPLC. The drug was well tolerated. Mean pharmacokinetic parameters for ofloxacin were Cmax 5.5 h (S.D. 1.97 h), Tmax 3.9 h (S.D. 3.25 h), T1/2 28 h (S.D. 17.37 h), AUC0-24 83.1 mg/1 h (S.D. 32.69 mg/l h). The desmethyl metabolite was produced in all patients but only half produced N-oxide. Cmax values were 0.21 mg/l (desmethyl) and 0.37 mg/l (N-oxide). Ofloxacin and desmethyl ofloxacin were variably and only slightly removed by haemodialysis whilst ofloxacin N-oxide was not removed at all. These results confirm that dosage reduction of ofloxacin is required in haemodialysis patients. Therapeutic drug monitoring by HPLC is recommended because of the observed variability in absorption and plasma half life.

Prostaglandin-dependent, frusemide-induced changes in renal plasma flow, glomerular filtration rate and plasma renin activity were measured in 14 patients with mild essential hypertension. The renal haemodynamic responses to frusemide were the same as in 10 normal subjects. Frusemide-induced changes in urinary PGE and kallikrein excretion were also the same as in normal subjects. Impaired renal release of vasodilator prostaglandins in essential hypertension is likely to be secondary to the hypertension rather than an underlying factor in its development.

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