Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacokinetics of aztreonam were studied in six healthy male subjects (group I) and 12 male patients with post-hepatitis liver cirrhosis and ascites. Patients were allocated into two groups according to serum creatinine; group II included nine patients with serum creatinine. < or = 15 mg/L while group III included three patients with serum creatinine > 15 mg/L. Aztreonam 1 g was given as iv bolus injection. Aztreonam reached a peak concentration in the ascitic fluid (AF) of 6.2 +/- 2.3 mg/L at 4 h, and of 8.7 +/- 4.4 mg/L at 6 h in groups II and III respectively. The level of the drug in AF 24 h post-dosing was still higher than MIC90 for Enterobacteriaceae in most patients. The half-life of elimination from serum increased significantly (P > 0.001) from 1.82 +/- 0.14 h in group I to 6.6 +/- 2.1 h and to 8.87 +/- 0.2 h in groups II and III, respectively. Both the central and the terminal volumes of distribution were higher in cirrhotic patients than in healthy volunteers. Liver cirrhosis and ascites resulted in a significant increase (P < 0.001) of the total body clearance (Cl) of aztreonam from 84 +/- 8 mL/h/kg in group I to 209 +/- 87 mL/h/kg in group II. However, the concomitant association of mild renal impairment in group III abolished this increase; Cl in group III was 122 +/- 50 mL/h/kg. The AUC0-infinity serum was 137.5 +/- 12.2, 78.5 +/- 24.9 and 151 +/- 42 mg.h/L in groups I, II and II, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacokinetics of aztreonam in patients with liver cirrhosis and ascites. 145 4

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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PMID:Evaluation of aztreonam in the treatment of spontaneous bacterial peritonitis in patients with cirrhosis. 353 Sep 45

Plasma concentrations of aztreonam follow a 2-compartment open model with a distribution half-life of 0.20 hours after intravenous injection. The volume of distribution at steady-state (Vss) after intravenous and intramuscular injection is about 0.16 L/kg (0.42 L/kg for free drug). After intramuscular injection, absorption is almost complete. Absorption after intraperitoneal administration in patients with peritonitis is 92%. Over a large dosage range, plasma concentrations increase dose proportionally. In healthy individuals, about 56% of the drug is plasma protein bound. Diffusion into tissues is generally slow, and the ratio between mean tissue and plasma aztreonam concentration seems to depend mainly on tissue composition. Aztreonam penetrates into cerebrospinal fluid (CSF) more rapidly in patients with inflamed meninges than in those with noninflamed meninges. Diffusion through the placenta is poor, as is diffusion into breastmilk. Aztreonam is predominantly eliminated by the kidney, partly by active tubular excretion. Extrarenal clearance appears to be through hepatic excretion. Metabolism occurs to a very limited extent. Total plasma clearance (CLp) in healthy adults is about 5.6 L/h and the terminal elimination half-life is 1.7 to 2.0 hours. CLp is similar in both children and adults when expressed as a function of bodyweight. However, in neonates, especially in low birthweight infants, CLp is lower. In various disease states, the Vss of aztreonam is not appreciably different from that found in healthy individuals. However, patients with low serum albumin levels (e.g. burn patients, critically ill patients and those with cirrhosis of the liver) generally have an increased volume of distribution. The elimination half-life of the drug is dependent on renal function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical pharmacokinetics of aztreonam. An update. 816 61