Pharmacokinetics of cefotaxime and desacetylcefotaxime in patients with liver disease

Ko, Richard J.; Sattler, Fred R.; Nichols, Sharon L.; Akriviadis, Evangelos; Runyon, Bruce A.; Appleman, Maria D.; Cohen, Jordan L.; Koda, Robert T.

doi:10.1128/aac.35.7.1376

Cited by 19 publications

(15 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The resulting cefotaxime typical CL value (11.1 L/h for a subject with ICU weight of 92 kg and with eCLcr of 94 mL/min) is in line with previously reported 10–13 L/h in patients with liver disease [ 23 ] and higher than 5.4 L/h in elderly patients [ 8 ]. Clearance of 15–17 L/h in healthy adult populations [ 21 , 22 ] is higher than in this ICU population as expected due to acute kidney injury in severe illness despite occasional cases of ARC.…”

Section: Discussionsupporting

confidence: 91%

Population pharmacokinetics of cefotaxime in intensive care patients

Swartling

Smekal

Furebring

et al. 2021

Eur J Clin Pharmacol

View full text Add to dashboard Cite

Purpose To characterise the pharmacokinetics and associated variability of cefotaxime in adult intensive care unit (ICU) patients and to assess the impact of patient covariates. Methods This work was based on data from cefotaxime-treated patients included in the ACCIS (Antibiotic Concentrations in Critical Ill ICU Patients in Sweden) study. Clinical data from 51 patients at seven different ICUs in Sweden, given cefotaxime (1000–3000 mg given 2–6 times daily), were collected from the first day of treatment for up to three consecutive days. In total, 263 cefotaxime samples were included in the population pharmacokinetic analysis. Results A two-compartment model with linear elimination, proportional residual error and inter-individual variability (IIV) on clearance and central volume of distribution best described the data. The typical individual was 64 years, with body weight at ICU admission of 92 kg and estimated creatinine clearance of 94 mL/min. The resulting typical value of clearance was 11.1 L/h, central volume of distribution 5.1 L, peripheral volume of distribution 18.2 L and inter-compartmental clearance 14.5 L/h. The estimated creatinine clearance proved to be a significant covariate on clearance (p < 0.001), reducing IIV from 68 to 49%. Conclusion A population pharmacokinetic model was developed to describe cefotaxime pharmacokinetics and associated variability in adult ICU patients. The estimated creatinine clearance partly explained the IIV in cefotaxime clearance. However, the remaining unexplained IIV is high and suggests a need for dose individualisation using therapeutic drug monitoring where the developed model, after evaluation of predictive performance, may provide support.

show abstract

Section: Discussionsupporting

confidence: 91%

Population pharmacokinetics of cefotaxime in intensive care patients

Swartling

Smekal

Furebring

et al. 2021

Eur J Clin Pharmacol

View full text Add to dashboard Cite

show abstract

“…Chronic liver disease affects drug disposition more than any other form of liver disease. For some drugs, such as cephalosporins, it has been reported that alterations in PK parameters in chronic parenchymal liver disease were highly correlated to clinical indices of hepatic impairment and the stages of liver impairment (Ko et al, 1991). More typically, however, the effects of liver diseases are unpredictable, lack sensitivity and do not correlate well with the type of liver damage, its severity, or liver laboratory test results (Davis, 2007).…”

Section: Hepatic Impairmentmentioning

confidence: 99%

Patient variation in veterinary medicine: part I. Influence of altered physiological states

Martinez

Modrić

2010

Journal of Veterinary Pharmacology and Therapeutics

View full text Add to dashboard Cite

Martinez, M., Modric, S. Patient variation in veterinary medicine: part I. Influence of altered physiological states. J. vet. Pharmacol. Therap.33, 213–226. In veterinary medicine, the characterization of a drug’s pharmacokinetic (PK) properties is generally based upon data that are derived from studies that employ small groups of young healthy animals, often of a single breed. These are also the data from which population predictions are often generated to forecast drug exposure characteristics in the target population under clinical conditions of use. In veterinary medicine, it is rare to find information on the covariates that can influence drug exposure characteristics. Therefore, it is important to recognize some of the factors that can alter the outcome of PK studies and therefore potentially alter the pharmacological response. Some of these factors are easily identified, such as breed, gender, age, and body weight. Others are less obvious, such as disease, heritable traits, and environmental factors. This manuscript provides an overview of the various stressors (such as disease, inflammation, pregnancy, and lactation) that can substantially alter drug PK. Part II of this series provides an overview of the potential impact of physiological variables such as age, weight, and heritable traits, on drug PK. Ultimately, failure to identify appropriate covariates can lead to substantial error when predicting the dose–exposure relationship within a population.

show abstract

“…CTX and d-CTX were found to interact synergistically against many microorganisms [17,19], allowing for possible dose reductions and for some CTX-resistant or moderately resistant organisms to be treated safely by high-dose CTX regimens [20]. CTX is mainly eliminated by the liver, and several authors have shown a prolonged serum half-life of CTX in cirrhotic patients [11,13,14]. The same phenomenon occurs in patients with reduced renal function in whom serum levels of CTX and d-CTX are much higher than in normal subjects, and the ratio of d-CTX to CTX increases significantly [9].…”

mentioning

confidence: 98%

Cefotaxime, Desacetyl‐Cefotaxime, and Bactericidal Activity in Spontaneous Bacterial Peritonitis

et al. 1999

View full text Add to dashboard Cite

We have prospectively studied 13 episodes of spontaneous bacterial peritonitis (SBP) in 12 patients treated with cefotaxime (CTX) 2 g intravenously every 8 h (mean duration, 5.3 days). Ascitic fluid was inoculated at the bedside. The cultures were done before, during (day 3 after CTX initiation), and 48-72 h (mean, 56 h) after the end of therapy. All SBP episodes were monomicrobial. During treatment, the concentrations of CTX and desacetyl-cefotaxime (d-CTX) in ascitic fluid were high in all 13 SBP episodes, and d-CTX was still present in 6 patients who had residual ascitic bactericidal titer (ABT) activity after the last dose of CTX. ABTs were >/=1:128 during CTX therapy in 12 episodes and were measurable in 7 patients after the last dose. All patients were cured. The present study provides scientific rationale to the clinical studies that suggest treating SBP episodes with lower doses of antibiotics and shorter treatment duration.

show abstract

Pharmacokinetics of cefotaxime and desacetylcefotaxime in patients with liver disease

Cited by 19 publications

References 22 publications

Population pharmacokinetics of cefotaxime in intensive care patients

Population pharmacokinetics of cefotaxime in intensive care patients

Patient variation in veterinary medicine: part I. Influence of altered physiological states

Cefotaxime, Desacetyl‐Cefotaxime, and Bactericidal Activity in Spontaneous Bacterial Peritonitis

Contact Info

Product

Resources

About