This study supports the extensive use of HAART in HIV-infected patients.

The pharmacokinetics of meropenem (ICI 194,660) and its open-ring metabolite (ICI 213,689) were studied in 6 healthy volunteers and 16 patients with moderate to severe renal impairment after a single intravenous dose of 500 mg given as a 30-min infusion. Concentrations of unchanged meropenem in plasma and urine were measured by both microbiological and high-pressure liquid chromatographic (HPLC) assays. A good correlation was found between the two techniques. Pharmacokinetic parameters of unchanged meropenem were determined by using the HPLC data. The terminal half-lfe of unchanged meropenem increased in relation to the degree of renal impairment, being 1.2 h in subjects with normal renal function and 10 h in patients with end-stage renal failure. Total body clearance and renal clearance of unchanged meropenem are lnearly related to creatinine clearance. The concentrations of the metabolite in plasma, which are very low in healthy subjects, signcantl increased in uremic patients. The apparent half-life of ICI 213,689 increased in uremic patients and was about 35 h in patients with severe renal insufficiency. Meropenem and its metabolite are effectively removed by hemodialysis. The dialysis clearance of the unchanged drug was 81 J 22 ml/min. Dosage adjustments of meropenem will be necessary in patients with severe renal impairment.Meropenem (ICI 194,660) is a new parenteral carbapenem antibiotic characterized by a broad antibacterial spectrum. It has been shown to have activity against both gram-positive and gram-negative pathogens, including anaerobes such as Bacteroidesfragilis. Meropenem is more active in vitro than imipenem against members of the family Enterobacteriaceae and Pseudomonas aeruginosa. Unlike imipenem, meropenem shows a good stability against human renal dehydropeptidase I and does not require the coadministration of a dehydropeptidase I enzyme inhibitor such as cilastatin (4,7,(9)(10)(11).The purpose of this study was to investigate the pharmacokinetics of meropenem (ICI 194,660) and of its open-ring metabolite (ICI 213,689) in patients with moderate or severe renal impairment after a single intravenous (i.v.) dose of 500 mg given as a 30-min infusion.

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The pharmacokinetics of ceftazidime, administered as a single intravenous dose of 15 mg/kg given in a bolus injection over 3 min, were investigated in 5 normal subjects and in 19 uremic patients. The subjects studied were divided into five groups according to values for endogenous creatinine clearance (CLCR): group I, five subjects with CLCR greater than 80 ml/min; group II, five patients with CLCR = 30 to 80 ml/min; group III, six patients with CLCR = 10 to 30 ml/min; group IV, four patients with CLCR = 2 to 10 ml/min; and group V, four anuric patients on hemodialysis. A two-compartment open model was used to calculate the pharmacokinetic parameters. In normal subjects, the mean apparent elimination half-life was 1.57 +/- 0.13 h. The central distribution volume and the apparent volume of distribution were 0.127 +/- 0.023 and 0.230 +/- 0.015 liter/kg, respectively. Of the injected dose, 83.6 +/- 3.6% was eliminated in the urine as parent drug within 24 h. The terminal half-life increased with impairment of renal function to about 25 h in severely uremic patients. Impairment of function did not significantly modify the half-life at alpha phase, central distribution volume, or apparent distribution volume. A 6- to 8-h hemodialysis procedure reduced concentrations of ceftazidime in plasma by approximately 88%, and the elimination half-life was 2.8 +/- 0.2 h. There was no evidence of accumulation of ceftazidime in four patients with severe and chronic impairment of function who received doses of 0.5 to 1.0 g every 24 h for 10 days.