Stuart Feldman

Pharmacokinetics of cefoperazone in the parturient.

Limited pharmacokinetic data for cefoperazone are available from the parturient. Because cefoperazone has a dual excretory pattern, primarily via the biliary system and secondarily via the kidney, pregnancy-induced physiologic alterations can influence its deposition and clearance. Twelve term parturients receiving cefoperazone prophylaxis after cesarean section were selected for study. After 2 g of cefoperazone was administered for 1 h intravenously, serial blood samples were assayed by high-pressure liquid chromatography. Plasma protein binding of cefoperazone was studied in vitro. The mean peak cefoperazone concentration +/- standard deviation was 169.9 +/- 60.4 micrograms/ml. The mean half-life was 152 min. Total serum clearance was 80.8 +/- 30.8 ml/min. The steady-state volume of distribution was 14.2 +/- 6.0 liters. All subjects had detectable trough levels at the end of the dosage interval, with a mean value of 6.5 +/- 5.2 micrograms/ml. Protein binding of cefoperazone for parturients was 74.3 +/- 10.9%, compared with 87.7 +/- 3.2% in nonpregnant controls (P less than 0.05). These data suggest that cefoperazone deposition can be greatly influenced by pregnancy. However, unlike several other new antimicrobial agents whose excretions are mainly renal, the cefoperazone half-life and thus trough concentration for the parturient more closely resemble that for the nonpregnant subject.

Clinical and pharmacokinetic evaluation of ticarcillin disodium plus clavulanate potassium in adolescent patients with malignancies

T he antipseudomonal penicillins have proved to be useful components of antimicrobial therapy in episodes of infection in adults and children with malignancies. Addition of the beta-lactamase inhibitor clavulanic acid to ticarcillin promises to expand this usefulness. We evaluated the clinical efficacy, safety, and pharmacokinetits of ticarcillin disodium plus clavulanate potassium in episodes of presumed infection among adolescent patients with malignancies.

Comparative pharmacokinetics of cefoxitin in postpartum normotensive and pregnancy-induced hypertensive patients

Limited pharmacokinetic data exist on cefoxitin, a semisynthetic cephamycin antibiotic, in the obstetric patient. Thirteen normotensive and five subjects with severe pregnancy-induced hypertension were identified within the first two postpartum days after cesarean section. After a 2 gm intravenous infusion, serial samples of blood were obtained and analyzed for cefoxitin by high-pressure liquid chromatography. Peak cefoxitin concentrations after infusion were 53.3 +/- 18.6 and 50.8 +/- 25.2 micrograms/ml for the normotensive and pregnancy-induced hypertensive groups, respectively. The only significant difference in pharmacokinetic parameters between these groups was a higher serum trough concentration of cefoxitin in the patients with pregnancy-induced hypertension as compared to the normotensive group. Because of diminished trough levels in our study patients, attention may need to be given to the adjustment of dosages in postpartum women with serious infections.

236 PHARMACOKINETICS OF AMIKACIN IN CHILDREN WITH MALIGNANCIES

Amikacin is an aminoglycoside antibiotic that is effective against gram negative bacilli which are resistant to other aminoglycoside antibiotics. Pharmacokinetic data of amikacin in pediatric patients are scant. The pharmacokinetics of amikacin were evaluated in 30 hospitalized children (5 to 14 years of age) with malignancies. Children receiving 15 or 20 mg/kg/24 hr administered every 8 to 6 hours, respectively had peak serum concentrations of 16.9±3.67 μg/ml (mean ± SD) at the end of a one hour infusion. Six and 8 hour serum concentrations were 1.27±1.26 and 0.64±0.92 μg/ml, respectively. The t½ was 78±43.8 minutes and the total clearance was 133±43 ml/min/1.73 m2. The mean volume of distribution was 0.26±0.08 1/kg. No accumulation of amikacin was noted and no side effects occurred. A 9% inactivation of amikacin occurred when incubated in normal donor sera at 37°C for 72 hours with varying concentrations of ticarcillin. Due to the rapid renal clearance and short half life of amikacin in these children, the currently recommended dose of amikacin should be increased and the frequency of administration shortened.