Penetration of cefpiramide and cefazolin into peritoneal capsular fluid in rabbits

Abstract

Penetration of cefpiramide and cefazolin into a specific extravascular fluid was measured with rabbits bearing capsules in the peritoneal cavity. A general feature of slow accumulation and elimination of drugs from extravascular sites having low surface area/volume ratios has also been observed in this study. The capsular concentration-time profiles were well expressed by the following equation: C(CF) = A(CF)[e-kel(CF)(t-to)-e-kp(CF)(t-to)], where C(CF), A(CF), kp(CF), kel(CF), and to indicate capsular concentration at time t, constant for the dimension of concentration, capsule penetration rate constant, capsule elimination rate constant, and lag time before penetration occurs, respectively. The kp(CF), kel(CF), and to were 0.139 h-1, 0.059 h-1, and 0.45 h, respectively, for cefpiramide, and 0.448 h-1, 0.0145 h-1, and 0.14 h, respectively, for cefazolin. A(CF) was 22.7 micrograms/ml for cefpiramide and 4.53 micrograms/ml for cefazolin, being parallel to the area under the plasma concentration-time curve for free drug from to to infinity (20.1 micrograms.h/ml for cefpiramide and 3.43 micrograms.h/ml for cefazolin). In conclusion, it is suggested that as well as kp(CF) and kel(CF), the area under the plasma concentration-time curve for free drug from to to infinity may play an important role regarding the circulating reservoir of drugs in determining capsular concentration-time profiles in experimental models for particular extravascular sites of infection, like abscesses into which drugs cannot easily penetrate.

Protein binding of cefazolin is saturable in vivo both between and within patients

“…Various studies in animals and humans support theconcept that the protein binding of cefazolin is concentration‐dependent (saturable) within the range of concentrations likely to be encountered clinically [8, 11–14]. However these studies were conducted using human plasma in vitro [8, 11] or in animals in vivo [12–14].…”

beta-Lactamase-mediated inactivation and efficacy of cefazolin and cefmetazole in Staphylococcus aureus abscesses

“…Previous studies with this model have demonstrated very slow elimination of cephalosporins from the capsule fluid (7,17), so it is unlikely that measuring the concentration in the capsule fluid at other times would have affected our results. Previous studies have demonstrated that cefazolin is 61.2 to 95% protein bound in rabbit serum at concentrations of 82 to 100 ,ug/ml (6,17), while cefmetazole is 53 to 59% protein bound at concentrations of 30 to 100 ,ug/ml (16,18).…”

“…Previous studies with this model have demonstrated very slow elimination of cephalosporins from the capsule fluid (7,17), so it is unlikely that measuring the concentration in the capsule fluid at other times would have affected our results. Previous studies have demonstrated that cefazolin is 61.2 to 95% protein bound in rabbit serum at concentrations of 82 to 100 ,ug/ml (6,17), while cefmetazole is 53 to 59% protein bound at concentrations of 30 to 100 ,ug/ml (16,18). Although we did not measure protein binding in our studies, the slightly higher level of protein binding of cefazolin measured previously would have favored higher steady-state cefazolin concentrations in the infected tissue site, since it is a protein-containing extravascular site (7,8,13).…”

Determination of cephazolin, ceftazidime, and ceftriaxone distribution in nucleus pulposus

“…Animal studies showed cephalosporin diffusion into the disc, and many factors influence the recovery of cephazolin from tissue samples [20,27]. The factors influence the recovery of cephazolin from tissue samples, including tissue protein binding [28], the selectivity of the solid-phase cartridge and the choice of medium for homogenization. In this study, ceftazidime had highest penetration in to NP tissue, and ceftriaxone had the lowest penetration in to NP tissue.…”