1 The antipyrine clearance and the urinary excretion of D-glucaric acid (D-GA) were determined in 122 patients receiving chronic anticonvulsant drug treatment and in 21 drug-free control subjects. 2 Patients treated with carbamazepine (CBZ), phenytoin (DPH), primidone (PMD) and phenobarbitone (PB), either alone or in combination, showed higher values of antipyrine clearance and excreted larger amounts of D-GA as compared to controls. While antipyrine clearance values did not differ significantly from one drug group to another, D-GA excretion was significantly higher in patients treated with CBZ than in those treated with DPH. 3 In patients treated with sodium valproate antipyrine clearance did not differ from control values. There was a trend for D-GA excretion to be higher in these patients but the difference was not statistically significant. 4 Significant positive correlations were found between the dosage of CBZ, DPH, PMD and PB and both indices of enzyme induction. These data demonstrate a dose-dependent degree of enzyme induction in patients receiving therapeutic doses of these anticonvulsants. The relative potency at average dose levels for antipyrine clearance was PB (1), DPH (0.92), CBZ (0.84), PMD (0.82) and for log D-GA excretion was PB (1), CBZ (0.96), PMD (0.95), DPH (0.90).

Serum concentrations of ciprofloxacin were reviewed in 22 patients given ciprofloxacin 400 mg intravenously 12 hourly for severe infection. No dosage modifications were made in patients with renal impairment. Patients who had either bowel or liver pathology in addition to renal failure had significantly higher serum concentrations than all other patients. Dosage reduction of ciprofloxacin in patients with severe sepsis and impaired renal function is not required unless they have co-existent intra-abdominal disease.

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1 The disposition kinetics of lignocaine and antipyrine were compared in eight normal subjects and in eleven patients receiving chronic therapy with antiepileptic drugs. The urinary excretion of Dglucaric acid (D-GA) was measured in 16 subjects. 2 In patients treated with antiepileptic drugs antipyrine clearance and D-GA excretion were significantly increased, whereas lignocaine bioavailability was significantly reduced. 3 When all the subjects included in the study were considered, a significant positive correlation could be found between the apparent oral clearance of lignocaine (Dose/area under the blood concentration curve) and both antipyrine clearance (r=0.73) and D-GA excretion (r=0.74). 4 When normal subjects and epileptic patients were considered separately, a significant positive correlation could be confirmed between the apparent oral clearance of lignocaine and both antipyrine clearance (r=0.71) and D-GA excretion (r=0.76) in normal subjects, and between antipyrine clearance and D-GA excretion (r=0.75) in epileptic patients. 5 These results suggest that the reduction of the oral availability of lignocaine in epileptic patients is secondary to induction of first-pass metabolism of the latter drug.

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