Pharmacokinetics and Pharmacodynamics of Cefpirome in Subcutaneous Adipose Tissue of Septic Patients

Abstract

The objective of the present study was to evaluate whether cefpirome, a member of the latest class of broadspectrum cephalosporins, sufficiently penetrates subcutaneous adipose tissue in septic patients. After the administration of the drug at 2 g, tissue cefpirome concentrations in septic patients (n ‫؍‬ 11) and healthy controls (n ‫؍‬ 7) were determined over a period of 4 h by means of microdialysis. To assess the antibacterial effect of cefpirome at the target site, the measured pharmacokinetic profiles were simulated in vitro with select strains of Staphylococcus aureus and Pseudomonas aeruginosa. The tissue penetration of cefpirome was significantly impaired in septic patients compared with that in healthy subjects. For subcutaneous adipose tissue, the area under the concentration-versus-time curve values from 0 to 240 min were 13.11 ؎ 5.20 g ⅐ min/liter in healthy subjects and 6.90 ؎ 2.56 g ⅐ min/liter in septic patients (P < 0.05). Effective bacterial growth inhibition was observed in all in vitro simulations. This was attributed to the significantly prolonged half-life in tissue (P < 0.05), which kept the tissue cefpirome levels above the MICs for relevant pathogens for extended periods in the septic group. By consideration of a dosing interval of 8 h, the values for the time above MIC (T > MIC) in tissue were greater than 60% for pathogens for which the MIC was <4 mg/liter in all septic patients. The present data indicate that cefpirome is an appropriate agent for the treatment of soft tissue infections in septic patients. However, due to the high interindividual variability of the pharmacokinetics of cefpirome in tissue, dosing intervals of not more than 8 h should be preferred to ensure that susceptible bacterial strains are killed in each patient.

Comparison of Fluconazole Renal Penetration Levels in Healthy and Candida albicans-Infected Wistar Rats

“…The results showed that FCZ recovery is concentration independent and inversely proportional to the flow rate, in agreement with previously reported data (20). Independent of the method employed, whether dialysis or retrodialysis, the FCZ recovery rate was around 50% in vitro as well as in vivo.…”

“…infections (20), this study was conducted to investigate, by microdialysis, FCZ penetration into the kidneys of healthy and Candida albicans-infected Wistar rats and to establish the relationship between total plasma and free renal levels of the drug.…”

Soft-Tissue Penetration of Ceftobiprole in Healthy Volunteers Determined by In Vivo Microdialysis

“…The degree of tissue penetration with ceftobiprole correlates well with other cephalosporins such as cefpodoxime (14), cefixime (14), cefpirome (10,21), and cefaclor (7) ( Table 2). There was a significant difference between the fAUC of plasma and the AUC of both tissues and between the AUC of muscle and the AUC of s.c. adipose tissue.…”

“…Also, free drug concentrations at the site of action/infection are much more relevant in determining efficacy (15,24), and exploring the concentration at the site of action has been recommended by regulatory agencies (1,2,8). One technique that has proven useful for the measurement of free-drug concentrations in subcutaneous (s.c.) adipose tissue and skeletal muscle is microdialysis (6,7,10,14,16,21).…”

Protein Binding of Antimicrobials: Methods for Quantification and for Investigation of its Impact on Bacterial Killing

“…The colonies are then counted and backextrapolated to the original volume to determine colony forming units per milliliter. For a more realistic simulation of in vivo PK, changing antibiotic concentrations in culture tubes for dynamic pharmacokinetic/ pharmacodynamic studies may be applied (74,75). This can either be provided by continuous adjustment or by means of a dynamic circulation model.…”