The comparative pharmacokinetics of ceftazidime and cefotaxime in healthy volunteers

Ceftazidime and the new SCE-2787 are parenteral cephalosporins with a broad antimicrobial spectrum. Pharmacokinetics, serum bactericidal activities, and side effects were investigated in a randomized crossover study. A total of 12 healthy volunteers received a 20-min infusion of 1.5 g of SCE-2787 or 2.0 g of ceftazidime. Serum and urine concentrations were determined by the bioassay method and by high-pressure liquid chromatography (HPLC) Infect. Dis. 136:196-204, 1977) against 40 clinically isolated strains. One hour after administration, we measured mean reciprocal bactericidal titers of SCE-2787 and ceftazidime, respectively, against Escherichia coli of 388 and 243, against KiebsieUla pneumoniae of 395 and 138, against Pseudomonas aeruginosa of 13.0 and 12.7, and against Staphylococcus aureus of 32.2 and 4.0. No severe side effects were observed in this single drug administration.

Section: Discussionsupporting

confidence: 90%

Comparative pharmacokinetics and serum bactericidal activities of SCE-2787 and ceftazidime

Paulfeuerborn

Müller

Börner

et al. 1993

“…This is in agreement with the results of previous studies showing ratios of between 0.65 and 0.97 (2). The combination of a ceftazidime/inulin clearance ratio of 0.72 and the previously reported low (17%) protein binding suggests that renal elimination of ceftazidime is almost completely mediated by glomerular filtration (10). A recent study with adults indicated that in addi- tion to glomerular filtration, some tubular excretion of ceftazidime, which is probably triggered by passive reabsorption, occurs (24).…”

Section: Discussionsupporting

confidence: 93%

Once-daily versus twice-daily administration of ceftazidime in the preterm infant

Anker

Schoemaker

Heijden

et al. 1995

Ceftazidime pharmacokinetics in 28 preterm infants (gestational ages, 25.6 to 31.9 weeks) were studied on day 3 of life. Patients with suspected septicemia were randomized on day 1 of life in two groups. One group (n ‫؍‬ 13) was administered 25 mg of ceftazidime per kg of body weight once daily, and the other (n ‫؍‬ 15) was given 25 mg of ceftazidime per kg twice daily. Both groups also received 25 mg of amoxicillin per kg twice daily. Blood samples were collected on day 3 of life with an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h after an intravenous bolus injection. An additional blood sample was taken at 24 h from the group dosed once a day. High-performance liquid chromatography was used to determine serum ceftazidime concentrations. The pharmacokinetics of ceftazidime were best described by using a one-compartment model. The half-life for the elimination of the drug from serum, apparent volume of distribution, total body clearance of ceftazidime, and inulin clearance were not significantly different for both groups. The ceftazidime/inulin clearance ratio was 0.72 for both groups. However, trough concentrations in serum for the twice-daily group were significantly (P < 0.001) higher (42.0 ؎ 13.4 mg/liter) than those for the once-daily group (13.1 ؎ 4.7 mg/liter). The latter concentrations were all still substantially higher than the MIC of ceftazidime for major neonatal pathogens. We conclude that the currently recommended dosage of 25 mg of ceftazidime per kg twice daily for preterm infants with gestational ages below 32 weeks may be adjusted during the first days of life to one daily dose at 25 mg/kg, provided that for the empirical treatment of septicemia, amoxicillin at 25 mg/kg is also given twice daily.Ceftazidime, an expanded-spectrum cephalosporin, is commonly used in the treatment of bacterial infections in the newborn (5). The currently recommended dosage regimen of ceftazidime for preterm infants less than 4 weeks old and whose birth weights are below 1,200 g is 25 to 100 mg/kg of body weight given intravenously twice daily (18). However, these dosage recommendations are based upon few pharmacokinetic data. Previous studies also did not stratify preterm infants according to gestational age (GA) or postnatal age, which has resulted in a substantial variability in pharmacokinetic parameters (3,(11)(12)(13)17). We have previously demonstrated that the pharmacokinetic behavior of ceftazidime in preterm infants is strongly dependent on GA and postnatal age. At a dosage of 25 mg of ceftazidime per kg given intravenously twice daily, high trough levels were observed, especially in infants with GAs below 32 weeks (21). High concentrations of beta-lactam antibiotics in serum and tissues do not result in a more rapid killing of bacteria (4), but they may lead to neutropenia and the impairment of cellular and humoral immune responses (14). We therefore designed a prospective randomized study to evaluate the pharmacokinetic effects of reducing the dosage of ceftazidime from 25 mg/kg twice daily to 25 m...

“…samples stored at -20°C. Ceftazidime was also stable in urine for 2 weeks at -20°C; however, in serum, especially at the lower concentrations, there was a small loss (<10%) of activity after 1 week, increasing to 22% after 2 weeks, and 73% after 4 weeks. Therefore, ceftazidime samples were assayed within 48 h, and moxalactam samples were assayed within 1 week.…”

mentioning

confidence: 91%

Comparative pharmacokinetics of ceftazidime and moxalactam

Tjandramaga¹,

Hecken²,

Mullie³

et al. 1982

The pharmacokinetics of ceftazidime and moxalactam were compared after intravenous and intramuscular administration of single 1-g doses to eight healthy volunteers in a crossover study. The bioavailability of the antibiotics after administration by either route was almost complete. Both drugs had similar areas under the serum curves. Significant differences between ceftazidime and moxalactam were observed with respect to the apparent volume of distribution (18.4 and 24.1 liters, respectively), to the terminal half-life (1.6 versus 2.0 h), and to urinary recovery of the active compound (96 versus 79%). Ceftazidime was almost completely eliminated by renal excretion (greater than 96%), whereas about 20% of the moxalactam was eliminated by nonrenal mechanisms. The concentrations of ceftazidime and moxalactam in serum after a 1-g dose exceeded the concentrations required to inhibit 90% of the Enterobacteriaceae for about 8 and 10 h, respectively. The levels of ceftazidime and moxalactam in serum exceeded the 90% minimal inhibitory concentration of Pseudomonas aeruginosa for about 6 and 1 h, respectively.