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Ertapenem, a Group 1 carbapenem, is a once-a-day parenteral beta-lactam antibiotic recently licensed in the USA and Europe. Monotherapy with ertapenem dosed as 1 g once a day has been shown to be highly effective in clinical trials for the treatment of complicated infections of skin and skin structures, complicated intra-abdominal infections, community-acquired pneumonia, acute pelvic infections and complicated urinary tract infections. Dosing modifications have not been recommended for adults on the basis of gender, age, weight or liver disease. Presently there are no data regarding the use of ertapenem in children. Dose reductions are indicated for patients with advanced renal insufficiency. Ertapenem is neither a substrate nor an inhibitor of P-glycoprotein or cytochrome P450 enzymes; significant drug interactions between ertapenem and drugs handled by these systems are not expected.

Trovafloxacin (CP-99,219) is a new fluoroquinolone antibacterial agent with a broad spectrum of activity against Gram-positive and Gram-negative bacteria. The pharmacokinetics and safety of trovafloxacin were characterised in healthy male volunteers after administration of single oral doses of 30, 100, 300, 600 and 1000 mg. trovafloxacin was rapidly absorbed and serum concentrations reached a maximum approximately 1 h after dosing. The corresponding mean Cmax values (mean +/- SD) were 0.3 +/- 0.0, 1.5 +/- 0.5, 4.4 +/- 1.1, 6.6 +/- 1.4 and 10.1 +/- 0.5 mg/L. Terminal-phase half-life was independent of dose, with an overall mean of 9.9 +/- 2.5 h. Generally, Cmax and AUC0-infinity increased linearly with dose. Less than 10% of the administered dose was recovered unchanged in urine. Over the dosing range, trovafloxacin renal clearance was fairly constant, averaging 0.67 +/- 0.36 L/h. Trovafloxacin binding to serum proteins was moderate (70%). Trovafloxacin was well tolerated at doses of 300 mg or below. There were no significant changes in the clinical chemistry or haematology parameters evaluated over the entire dosing range.

Twenty patients (mean age 52 +/- 12 years, mean weight 75 +/- 15 kg) scheduled for elective myelogram or spinal anaesthesia were enrolled to determine the cerebrospinal fluid (CSF) penetration of a new expanded spectrum cephalosporin antibiotic, cefpirome (HR-810). A single 2 g intravenous dose of cefpirome was administered as a bolus between 1 and 8 h before lumbar puncture. Blood samples were collected at 15 pre-determined times and a single CSF sample was obtained at the time of lumbar puncture. Serum and CSF cefpirome concentrations were determined by high performance liquid chromatography. The mean maximal serum concentration of cefpirome was 264 +/- 76 mg/L. A mean steady-state volume of distribution of 20 +/- 4 L, clearance of 7.4 +/- 1.3 L/h, and half-life of 2.5 +/- 0.5 h were determined. Mean CSF concentrations were 0.50 +/- 0.11 mg/L at 1-2 h post dose (n = 4), 0.57 +/- 0.13 mg/L at 2-4 h post dose (n = 4), 0.76 +/- 0.34 mg/L at 4-6 h post dose (n = 7), and 0.83 +/- 0.29 mg/L at 6-8.3 h post dose (n = 5). Blood:brain barrier permeability to cefpirome may not be a limiting factor as CSF concentrations were rapidly attained. Further studies are required to determine the mechanism of cefpirome transport between plasma and CSF.

Interaction between ciprofloxacin and theophylline was studied in eight male volunteers, who were randomly divided into two groups. All subjects were given intravenous theophylline and indocyanine green (ICG) on study days 0, 7 and 14. Group I subjects received ciprofloxacin 750 mg orally every 12 h on days 1-7. Group II subjects received ciprofloxacin 750 mg every 12 h on days 6-14. No significant changes in ICG clearance or half-life were noted. A significant increase in theophylline half-life and volume of distribution was observed (P less than 0.05); however, clearance was not significantly decreased (P = 0.1). A potentially clinically significant interaction was detected in three subjects whose theophylline clearance decreased by 42-113%. Until further clinical experience is gained, we advise caution when these agents are coadministered. Some adjustment in theophylline dosage may be required; therefore, these patients should have serum theophylline concentration measurements and careful clinical assessment for theophylline toxicity.

The effect of renal impairment on the single dose pharmacokinetics of oral enoxacin was studied in 28 volunteers with creatinine clearances ranging from less than 15 to 120 ml/min, including patients undergoing chronic haemodialysis. Following an overnight fast, 400 mg of enoxacin was administered orally to each subject. Blood and urine samples were collected at predetermined times for 48 and 72 h, respectively. Plasma and urine samples were assayed for enoxacin and for oxo metabolite concentrations by a specific high performance liquid chromatographic method. Area under the concentration-time curve from time 0 to infinity (AUC0-infinity) was increased in subjects with renal impairment. Plasma half-life (10.6-11.6 h) in volunteers with severe renal impairment was approximately double the 5.2 h half-life found in subjects with normal renal function, and this should result in steady-state enoxacin concentrations approximately double those measured in normal subjects given equivalent doses. Haemodialysis did not remove significant amounts of enoxacin. A significant correlation between creatinine clearance and enoxacin renal clearance was observed (r = 0.97).