Pharmacokinetics of cefazolin in patients with normal and impaired renal function

Bergan, Tom; Brodwall, E. K.; Orjavik, O

doi:10.1093/jac/3.5.435

Cited by 19 publications

(16 citation statements)

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“…This is consistent with the common trend used for cefazolin PK analysis found in the literature (10). In our study, the volume of distribution and clearance values for cefazolin (Table 2) were in good agreement with the values reported in the literature for nonpregnant and pregnant adults (9,(28)(29)(30)(31)(32).…”

Section: Discussionsupporting

confidence: 91%

Pharmacokinetics of Prophylactic Cefazolin in Parturients Undergoing Cesarean Delivery

Elkomy

Sultan

Drover

et al. 2014

Antimicrob Agents Chemother

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The objectives of this work were (i) to characterize the pharmacokinetics of cefazolin in pregnant women undergoing elective cesarean delivery and in their neonates; (ii) to assess cefazolin transplacental transmission; (iii) to evaluate the dosing and timing of preoperative, prophylactic administration of cefazolin to pregnant women; and (iv) to investigate the impact of maternal dosing on therapeutic duration and exposure in newborns. Twenty women received 1 g of cefazolin preoperatively. Plasma concentrations of total cefazolin were analyzed from maternal blood samples taken before, during, and after delivery; umbilical cord blood samples obtained at delivery; and neonatal blood samples collected 24 h after birth. The distribution volume of cefazolin was 9.44 liters/h. The values for pre-and postdelivery clearance were 7.18 and 4.12 liters/h, respectively. Computer simulations revealed that the probability of maintaining free cefazolin concentrations in plasma above 8 mg/liter during scheduled caesarean surgery was <50% in the cord blood when cefazolin was administered in doses of <2 g or when it was administered <1 h before delivery. Therapeutic concentrations of cefazolin persisted in neonates >5 h after birth. Cefazolin clearance increases during pregnancy, and larger doses are recommended for surgical prophylaxis in pregnant women to obtain the same antibacterial effect as in nonpregnant patients. Cefazolin has a longer half-life in neonates than in adults. Maternal administration of up to 2 g of cefazolin is effective and produces exposure within clinically approved limits in neonates.

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Section: Discussionsupporting

confidence: 91%

Pharmacokinetics of Prophylactic Cefazolin in Parturients Undergoing Cesarean Delivery

Elkomy

Sultan

Drover

et al. 2014

Antimicrob Agents Chemother

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“…In rats, 8% of a cefo taxime dose was normally eliminated via bile and this was increased 10-fold in nephrectomizcd animals [12]. We [6] have ob served a similar pattern with ccfazoline for a large number of patients for which a bilogarithmic relationship between t'/a and Cl, applied to glomerular filtration rates above lOml/min. Below this level, there was a levelling off to the effect that the maximum t1/» was considerably below that suggested by the regression line for better renal functions.…”

Section: Discussionmentioning

confidence: 84%

Pharmacokinetics of a New Cephalosporin, Cefotaxime (HR 756) in Patients with Different Renal Functions

Bergan¹,

Larsen

Brodwall

1982

Chemotherapy

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The pharmacokinetics of intramuscular doses of 1.0 g cefotaxime (HR 759) was studied in 19 persons with normal or reduced renal function. Quantitation was done by both microbiological and high pressure liquid chromatography (HPLC) methods. The HPLC determined unchanged cefotaxime and desacetyl cefotaxime and up to 2 more metabolites in serum, whether unchanged or biotransformed. Patients with renal functions within the normal range (inulin clearance above 100 ml/min) had a mean serum peak concentration of 24.5 ± 10.5 μg/ml. In renal failure, both serum concentrations and the terminal serum half-life (t½β) increased. The mean terminal serum half-life was 2.1 h according to the microbiological assay and 1.5 h according to the HPLC procedure at a glomerular filtration rate (GFR) of 100 ml/min. At an inulin clearance of 10 ml/min, the serum half-life was 6.0 h for the total microbiologically assayed activity and 3.6 h for unchanged drug. There is a linear relationship between log serum half-life of the three moieties of unchanged cefotaxime, total antimicrobial activity (agar diffusion assay with Escherichia coli as indicator), and the major metabolite desacetyl cefotaxime and log clearance of both inulin (Cl_I) and p-amino-hippuric acid (CI_PAH) down to CI_I^, of 10 ml/min. The excretion of unchanged drug in urine during 24 h was reduced gradually upon reduction in renal function from a mean of 59.4 ± 10.2% (range 52.1–77.1) in 5 subjects with GFR above 100 ml/min. The area volume of distribution, e.g. the area of the one-compartment linear open model or during the β-phase of the two-compartment model, V_d,area, was 34.3 ± 10.4 litres according to the microbiological assay and 27.3 ± 13.4 litres for unchanged cefotaxime in patients with renal function within the normal range. The patients with reduced renal function had only insignificantly different distribution volumes. The volumes in normal individuals correspond to 53% of the body weight. The deasacetyl cefotaxime metabolite is excreted more slowly than the parent compound and elimination is relatively longer compared to the parent compound in patients with reduced renal functions. Doses for patients with reduced renal function are discussed. Because nonrenal mechanisms of elimination assume importance when the renal route becomes inefficient, elimination is only moderately prolonged, even in patients with severe renal impairment. Therefore, only moderate reduction in dosage seems necessary.

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“…19 The distribution volume for cefazolin was 10 to 12 L, 17,20,21 approximately, which was smaller than for other cephalosporins. 19,22 Cefazolin is widely distributed into most body tissues and fluids including the gallbladder, liver, kidneys, bone, sputum, bile, pleural, and synovial fluid; however, CSF penetration is poor.…”

Section: Pharmacokineticsmentioning

confidence: 86%

“…1,17,18 For the intravenous route, it was slightly shorter, approximately 1.5 hours, compared with the intramuscular route (Fig. 2).…”

Section: Pharmacokineticsmentioning

confidence: 96%

“…18 More precisely, Bergan proposed a dose adjustment as intramuscular 500 mg administration with 8-hour intervals when creatinine clearance is above 60 ml/min, with 12-hour intervals for creatinine clearance of 30-60 ml/min, with 24-hour intervals for creatinine clearance of 15-30 ml/min, and at 36-hour intervals for creatinine clearance of less than 15 ml/min. 17 In hemodialysis patients, Marx et al proposed that approximately 20 mg/kg of cefazolin administered post-hemodialysis appears to be a safe and effective empiric therapy. 28 Sowinski et al proposed that 15 or 20 mg/kg after hemodialysis maintained appropriate serum concentration of cefazolin throughout a 2-3-day interdialytic period.…”

Section: Renal Impairmentmentioning

confidence: 99%

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Safety and Efficacy of Cefazolin Sodium in the Management of Bacterial Infection and in Surgical Prophylaxis

Kusaba

2009

Clinical Medicine. Therapeutics

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Abstract:Cefazolin sodium is a first-generation cephalosporin antibiotic and has been used worldwide since the early 1970s. It is used for the treatment of bacterial infections in various organs, such as the respiratory tract, skin and skin structure, genital tract, urinary tract, biliary tract, and bone and joint infections. It has also been used for septicemia due to susceptible gram-positive cocci (except Enterococcus), some gram-negative bacilli including E. coli, Proteus, and Klebsiella may be susceptible, and for perioperative prophylaxis. After the introduction of penicillins and other cephalosporins, occasional outbreaks of methicillin-resistant Staphylococcus aureus were noted. As a result, vancomycin use was increased; however, very recently and most alarmingly, vancomycin-resistant strains have been described. In this setting, to avoid the risk of the development of vancomycin-resistant strains further, vancomycin use should be curtailed. In consideration of this historical background, the appropriate use of antibiotics, such as dosage, dosage intervals, and the duration of administration is required not only for the protection of patients' health but also for the prevention of the development of drug resistance. Cefazolin has been used in clinical practice for about 40 years, and a large body of evidence has been accumulated, and its efficacy and safety are well established compared with other antibiotics. Therefore, cefazolin has been chosen as a first-line anti-microbial for prophylaxis after various surgical procedures, including cardiovascular surgery, hysterectomy, arthroplasty and so on. Based on these facts, especially for the prophylaxis of surgical site infections, the first-generation cephalosporin, cefazolin, is now being "re-visited".

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Pharmacokinetics of cefazolin in patients with normal and impaired renal function

Cited by 19 publications

References 0 publications

Pharmacokinetics of Prophylactic Cefazolin in Parturients Undergoing Cesarean Delivery

Pharmacokinetics of Prophylactic Cefazolin in Parturients Undergoing Cesarean Delivery

Pharmacokinetics of a New Cephalosporin, Cefotaxime (HR 756) in Patients with Different Renal Functions

Safety and Efficacy of Cefazolin Sodium in the Management of Bacterial Infection and in Surgical Prophylaxis

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