Effects of cirrhosis on kinetics of aztreonam

MacLeod, Catherine; Bartley, E A; Payne, John A.; Hudes, Ellen; Vernam, K; Devlin, RG

doi:10.1128/aac.26.4.493

Cited by 25 publications

(5 citation statements)

References 19 publications

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“…In one study, extrarenal clearance of aztreonam in patients with alcoholic cirrhosis of the liver was significantly lower than in healthy controls or in patients with post-biliary cirrhosis (MacLeod et al 1984). In patients with biliary obstruction, biliary concentrations of aztreonam were extremely low (Martinez et al 1984).…”

Section: Pharmacokinetics In Liver Failurementioning

confidence: 97%

Clinical Pharmacokinetics of Aztreonam

Mattie

1988

Clinical Pharmacokinetics

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Aztreonam (azthreonam) is practically completely absorbed after intramuscular injection. After intravenous injection plasma concentrations follow a 2-compartment open model, with a t1/2 alpha of 0.20 hours. Volume of distribution at steady-state (Vdss) after intravenous or intramuscular injection is about 0.16 L/kg (0.42 L/kg for the free drug). After oral administration less than 1% of the drug is absorbed. Over a large dosage range plasma concentrations increase linearly with dose. No accumulation occurs after multiple dosing. Plasma binding in healthy subjects is about 56% and is not concentration dependent. Diffusion into tissues is generally slow, and the ratio between mean tissue and plasma concentration seems to depend mainly on the composition of the tissue. In inflamed meninges, penetration of aztreonam into CSF is more rapid than with uninflamed meninges. Diffusion through the placenta is poor, as is diffusion into breast milk. The main route of elimination of aztreonam is by the kidney, partly by active tubular excretion, but this can be inhibited by probenecid. Extrarenal clearance is probably due to excretion by the liver. Metabolism occurs to a very limited extent. Total plasma clearance in healthy adults is about 140 ml/min (8.4 L/h) or 2 ml/min/kg (0.12 L/h/kg), and terminal half-life is 1.7 hours. In children clearance is similar to that in adults when expressed as a function of bodyweight, but in neonates, especially in low birthweight infants, it is less [about 1 ml/min/kg (0.06 L/h/kg)]. In various disease states the Vdss of aztreonam is not appreciably different from that found in healthy individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Pharmacokinetics In Liver Failurementioning

confidence: 97%

Clinical Pharmacokinetics of Aztreonam

Mattie

1988

Clinical Pharmacokinetics

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“…Both the volume of distribution and the clearance of pefloxacin were reduced in cirrhotic patients, especially when ascites were present (3,6). The half-life of aztreonam increased in patients with either alcoholic or biliary cirrhosis, due to reduced serum clearance (15). A decrease in the plasma protein binding of erythromycin in cirrhotic patients led to an increase in the volume of distribution; the decreased binding was accompanied by a decrease in the nonrenal free clearance (1).…”

Section: Discussionmentioning

confidence: 93%

Pharmacokinetics of intravenous cefetamet and oral cefetamet pivoxil in patients with hepatic cirrhosis

Hayton

Kneer

Blouin

et al. 1990

Antimicrob Agents Chemother

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The pharmacokinetics of orally administered cefetamet pivoxil and intravenously administered cefetamet were studied in 12 healthy subjects and 12 patients with hepatic cirrhosis without ascites. Cirrhosis had no detectable effect on the pharmacokinetics of cefetamet and on the bioavailablity of cefetamet pivoxil. After intravenous cefetamet in control versus cirrhotic subjects, respectively, the following mean ± standard deviation values were observed: total body clearance, 128 + 10.2 versus 123 + 28.8 mi/min; steady-state volume of distribution, 23.2 ± 2.2 versus 22.7 + 4.6 liters; half-life, 2.42 ± 0.21 versus 2.35 ± 0.41 h. Renal and nonrenal clearances of cefetamet were similar in both groups, as were the mean residence times and areas under the plasma concentration-time curve. For oral cefetamet pivoxil, no differences were detected in the mean values of the percentage of dose absorbed: 44.6 + 9.1 versus 50.1 + 12.9. The rate of appearance of cefetamet in the plasma also was not affected by cirrhosis: similar mean values were found for the mean residence time and the maximum concentration in plasma and its time of occurrence.

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“…The pharmacokinetics of aztreonam have been described using an open, twocompartmental model in healthy subjects (12,(21)(22)(23). A prolonged half-life (mean = 3.2 hr) and higher trough serum levels after 8 hr (mean = 7.6 pg per ml) associated with a decreased nonrenal clearance (mean = 0.2 ml per min per kg) have been reported after administration of a single dose of aztreonam in cirrhotic patients (24). While in our patients the trough serum levels were also very high (mean = 27 pg per ml), the peak serum levels (mean = 61.9 pg per ml) were similar to those reported in healthy subjects, probably because of the large distribution volume related to ascites.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of aztreonam in the treatment of spontaneous bacterial peritonitis in patients with cirrhosis

et al. 1986

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To determine the efficacy of aztreonam in the treatment of spontaneous bacterial peritonitis in patients with hepatic cirrhosis, 14 patients (7 males, 7 females) with 16 Gram-negative infective episodes (12 Escherichia coli and 4 Klebsiella pneumoniae) were treated with aztreonam infusions at doses of 1 gm per 8 hr for a planned 14-day period. Ages ranged from 40 to 75 years with a mean of 57 +/- 10 years. All organisms were highly susceptible to aztreonam (minimal inhibitory concentration less than or equal to 0.06 to 0.12 micrograms per ml). Serum antibiotic levels were 61.9 +/- 25.5 micrograms per ml (peak) and 27 +/- 18.5 micrograms per ml (trough). Ascitic fluid antibiotic levels were 33.6 +/- 22.5 micrograms per ml (peak) and 32.7 +/- 16.8 micrograms per ml (trough). Although the symptoms of infection were controlled within 3 days and ascitic fluid cultures became negative after 48 hr, 10 patients (62.5%) died, with hepatorenal syndrome and digestive tract hemorrhage as the principal causes of death. Three patients developed streptococcal superinfections during treatment; Streptococcus faecalis peritonitis in one case and spontaneous bacteremia due to Streptococcus equinus and Streptococcus mutans in the other two. Aztreonam was well tolerated and clinically and bacteriologically efficacious in controlling the infection. Serum and ascitic fluid levels were considerably higher than the minimal inhibitory concentration for the causative organisms, suggesting that lower doses may achieve suitable therapeutic levels. A negative aspect of the antibiotic therapy was the superinfections. The high mortality rate was attributable to the generally poor underlying condition of the patients.

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Effects of cirrhosis on kinetics of aztreonam

Cited by 25 publications

References 19 publications

Clinical Pharmacokinetics of Aztreonam

Clinical Pharmacokinetics of Aztreonam

Pharmacokinetics of intravenous cefetamet and oral cefetamet pivoxil in patients with hepatic cirrhosis

Evaluation of aztreonam in the treatment of spontaneous bacterial peritonitis in patients with cirrhosis

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