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The quinolone antibiotic lomefloxacin was administered as a 400 mg single oral dose to 12 subjects with renal impairment (creatinine clearance 5-65 mL/min/1.73 m2) and to 13 healthy subjects (creatinine clearance 80-135 mL/min/1.73 m2). The concentrations of lomefloxacin in plasma and urine were determined by high-pressure liquid chromatography up to 48 hours post-administration. Linear correlations were found between lomefloxacin plasma and renal clearances and creatinine clearance. The mean nonrenal clearance of lomefloxacin (approximately 32 mL/min/1.72 m2) was not influenced by renal function. The mean plasma clearances of lomefloxacin in healthy subjects and in a subgroup of patients with severe renal impairment (creatinine clearance 5-15 mL/min/1.73 m2) were 209 and 43 mL/min/1.73 m2, respectively. The decrease in plasma clearance of lomefloxacin was explained fully by the decrease in renal clearance. The elimination half-life of lomefloxacin increased significantly with the degree of renal impairment, from 7.5 hours in normal subjects to 26.9 hours in subjects with severe renal impairment. The maximum serum concentration and the time to maximum serum concentration were not significantly affected by renal function. The pharmacokinetics of lomefloxacin are dependent on renal function, and appropriate dosage adjustment is necessary when creatinine clearance is less than 30 mL/min/1.73 m2.

Labetalol (Trandate) is a new antihypertensive agent with both alpha- and beta-adrenoceptor blocking properties. In a double-blind cross-over study the antihypertensive action and side-effects of labetalol and propranolol were compared in 18 previously untreated outpatients with hypertension, WHO stage I--III. Mean daily dose of labetalol was 667 mg and of propranolol 129 mg. Labetalol reduced systolic and diastolic blood pressure in the seated and upright position significantly more than propranolol. The pulse rate reduction was greater with propranolol. Side-effects were more pronounced with propranolol. The antihypertensive effect, effect on pulse rate and pharmacokinetics of a single oral dose of 400 mg labetalol were studied in 6 patients with normal and 6 patients with impaired renal function (creatinine clearance less than 20 ml/min), all belonging to WHO stage I--II. A significant fall in pulse rate and systolic and diastolic blood pressure was observed in both groups, the duration being more than 25 h. No difference was found between the two groups. From the serum concentration-time curves the elimination rate constant, elimination half-life and area under the curve were calculated. The mean values of the two groups did not differ significantly. A pronounced interindividual variation was found in both groups.

We have studied the pharmacokinetics of ceftazidime in 37 patients suffering from serious bacterial infections. All the patients had impairment of renal function and received moderate to high doses of frusemide concurrently. The doses of ceftazidime were given according to renal function as recommended by the manufacturer. Serum and urine samples were frequently collected, and drug concentrations measured by high performance liquid chromatography. The patients were grouped and evaluated according to renal function, mean (SD) creatinine clearances ranging from 70.1 (12.4) to 11.0 (3.2) ml.min-1. The pharmacokinetics of ceftazidime depended on renal function. A statistically significant increase in ceftazidime elimination half-life and decreases in urinary recovery, total body clearance, and renal clearance in proportion to the decrease in renal function were observed (p less than 0.05). The apparent volume of distribution also increased, but not significantly (p greater than 0.05). A linear correlation was found between the total body and renal clearances of ceftazidime and creatinine clearance. The extrarenal clearance increased from 3.9 to 14.0 ml.min-1 with decreasing renal function. Concurrent treatment with ceftazidime and moderate to high doses of frusemide did not impair renal function and no evidence of nephrotoxicity was found.

The pharmacokinetics and clinical effects of cefuroxime were investigated in 5 patients with severe impairment of renal function (creatinine clearance less than or equal to 23 ml/min), suffering from an urinary tract infection. Bolus i.v. injections of cefuroxime 750 mg b.i.d. or 750 mg once daily were given to the patients depending on the degree of renal impairment. The concentration of drug in serum and urine was measured during treatment, and pharmacokinetic parameters were evaluated on the second and last days; the parameters obtained on the 2 days did not differ significantly. Drug elimination half-life increased from 4.2 h (creatinine clearance 23.0 ml/min) to 22.3 h (creatinine clearance 5.0 ml/min) with decreasing renal function. The apparent volume of distribution ranged from 11.6 to 17.9 l, and showed a substantial increase to 29.6 l in the patient with the poorest renal function. A linear correlation was found between the total and renal clearance of cefuroxime and the creatinine clearance; the extrarenal clearance was 8.24 ml/min. Concomitant treatment with furosemide did not impair renal function and no evidence of nephrotoxicity was found. The clinical efficacy of the drug was good. Symptoms of infection subsided after 3-4 days and the isolated pathogens were eradicated. No relapse or episodes of reinfection were observed in a following-up period of 3 months. The drug was well tolerated and no side effects or changes in haematological or biochemical values were seen.