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Imipenem serum pharmacokinetics, lung tissue and pericardial fluid concentrations were measured in 10 patients undergoing thoracotomy, following a 1 g intravenous infusion of imipenem-cilastatin. The serum concentrations of imipenem 0.5 h and 4 h after the end of the 40 min infusion were 53.3 (+/- 16.7) and 2.0 (+/- 0.3) mg/l, respectively. The concentration of imipenem in lung tissue at 1 h was lower than in pericardial fluid and at 2.25 h the mean concentration of imipenem in pericardial fluid was 10.5 mg/l, vs. 0.28 mg/kg of lung tissue. Imipenem concentrations in pericardial fluid remained above 5 mg/l, well above the MIC for most pathogens, for 1 h whereas in pericardial fluid the concentration was 10.5 mg/l at 2.25 h.

The penetration of ceftazidime in pericardial fluid and lung tissue was investigated in 14 thoracotomized patients, who had normal renal function and did not receive any antibiotic treatment before thoracotomy. The drug (28 mg/kg) was given by i.v. Blood, pericardial fluid and lung tissue samples were taken over the next 5 hours. Concentrations of ceftazidime in the lung tissue were very high in the first hour and over the 200 and 300 min time interval, the ratio between serum and lung tissue levels was 0.7. The correlation coefficient between pericardial fluid, serum ratio and time was calculated to be of 0.99 (P less than 0.001). From these data we can observe that ceftazidime rapidly diffuses into the pericardial space and lung tissue where good concentrations (5.4 mcg/g) persist for at least 5 hours.

The relationship between concentrations in serum and levels in tissue of flurithromycin, a new fluorinated macrolide, was determined in patients undergoing maxillofacial surgery and thoracotomy. All patients received 500 mg of flurithromycin orally every 8 h. Drug levels in serum, bone, soft tissue, lung, and pericardial fluid were determined microbiologically. The total amount of antibiotic per gram of tissue was calculated on the basis of the concentration in the supernatant of the homogenate. From the parallel course between free concentrations in serum and calculated contents in interstitial fluid tissue, it was concluded that the tissues examined were easily accessible by flurithromycin; penetration values measured by the ratio of areas under the curve were 8.3 for lung, 3.6 for bone, and 0.8 for soft tissue. The results of the pharmacokinetic study suggest that accumulation of the drug during repetitive multiple doses is predictable. Mean residence times were 10.2 and 8.3 h in groups 1 and 2, respectively. For bacteriostatic drugs such as macrolides, not only very high but also prolonged concentrations in tissue lead to favorable therapeutic result.