[Antibiotic concentration during extracorporeal circulation (author's transl)].

In open surgery, ampicillin (Solcillin) or cephacetrile (Celtol), 2 g for patients weighing 20 kg or more, and 1 g for those below 20 kg, was administered, and the antibiotic concentrations in blood and urine were estimated during extracorporeal circulation, from the time of operation to the admission in an intensive care unit (Group A). In other group, a total circulation volume of 0.3 mg/ml of the antibiotic was administered, based on body weight of patients and priming volumes (Group B). In Group A, blood concentration of antibiotics was so variable that it was difficult to decide additional dosage. In Group B, comparatively definite concentrations were estimated in each case. In extracorporeal circulation for a long time, it is preferable to maintain the blood concentration of antibiotic at 50 micrograms/ml, by additional antibiotic administration 90 approximately 120 minutes after the beginning of the extracorporeal circulation. In patients with preoperative subacute bacterial endocarditis, the blood concentration should be kept over 100 micrograms/ml during extracorporeal circulation.

Cephacetrile--application of pharmacokinetic data to dosage determination.

This pharmacokinetic investigation was based on the determination of serum and urinary levles of cephacetrile in 50 subjects given single intramuscular or intravenous doses of 0.5 or 1 gm of the antibiotic; 30 normal subjects, 10 patients with renal insufficiency, and 10 patients with chronic nephritis undergoing maintenance haemodialysis were included in this study. In normal subjects, mean serum half-life was 1.09 hours (Ke = 0.6337) after intramuscular injection of 0.5 gm cephacetrile, 1.31 hours (Ke = 0.5276) after intramuscular injection of 1 gm, and 0.89 hours (Ke = 0.7806) after intravenous injection of 1 gm. Absorption half-life was 0.45 hours after intramuscular injection of 1 gm cephacetrile. The urinary elimination of cephacetrile over the first 6 hours after injection was on the average 72.7% of the administered dose. After intravenous injection of 1 gm of the antibiotic, the plasma clearance of cephacetrile was 407 ml/min., and its renal clearance 313 ml/min. A linear correlation was found between the values of overall elimination rate constant (Ke) and creatinine clearance in the subjects under investigation (Ke = 0.0080 + 0.0061 ClCr). The established pharmacokinetic characteristics were used to calculate the maintenance and loading doses as well as the intervals between injections adjusted to creatinine clearance. These data constitute true dosage schemes adapted to the particular case of each patient according to his kidney function.