Pharmacokinetics Of Cefpirome Research Articles

Pharmacokinetics of cefpirome following intravenous and intramuscular administrations in healthy and febrile sheep (Ovis aries)

Cefpirome is fourth generation cephalosporin class of drug, which facilitates rapid penetration through the outer membrane of Gram-negative bacteria and results in potent activity against Gram-negative pathogens. As fever is one of the most common manifestations in bacterial diseases, the study was undertaken to investigate pharmacokinetics of single dose intravenous and intramuscular administrations of cefpirome (10 mg/kg of body weight) in healthy and lipopolysaccharide (LPS) induced febrile sheep and to perform PK-PD analysis using MIC values reported in previous studies and the pharmacokinetic parameters obtained in this study. Following intravenous and intramuscular administrations of cefpirome in healthy sheep, the plasma drug concentration was detected up to 12 h, while plasma drug concentration was detected up to 18 h following intravenous and intramuscular administrations in febrile sheep. Induction of febrile state significantly altered pharmacokinetic profile of cefpirome following intravenous and intramuscular administrations in sheep. Based on pharmacokinetic- pharmacodynamic integration, an optimal intramuscular dosage regimen of 10 mg/kg once daily for cefpirome in febrile sheep was predicted for targeted average MIC of ≤ 0.25 µg/mL.

Pharmacokinetics of Cefpirome Following Intravenous and Intramuscular Administration in Cow Calves

Background: Cefpirome is a broad-spectrum semi synthetic β-lactamase resistant fourth generation cephalosporin. Looking to potential for clinical use, pharmacokinetics of cefpirome following intravenous and intramuscular administration (10 mg kg ) in cow calves was determined. Methods: Cefpirome concentration in plasma samples was 1 determined by reverse-phase high performance liquid chromatography with mobile phase. The mobile phase was a mixture of 0.2 M sodium acetate (3.5%), acetronitrile (17.5%) and HPLC water (79%) with a pH of 5.1. Mobile phase was filtered by 0.45 µ filters and pumped into column at a flow rate of 1.0 mL min at ambient temperature. The 1 effluent was monitored at 258 nm wavelength. Results: Following intravenous administration of the cefpirome in goats, volume of distribution at steady-state (Vd ), elimination half-life (t ) and total body clearance (Cl ) wer e ss 1/2β B reported 0.33±0.01 L kg , 2.41±0.23 h and 2.36±0.18 mL min kg , respectively. Following intramuscular 1 1 1

Abscess penetration of cefpirome: concentrations and simulated pharmacokinetic profiles in pus

Abscess patients frequently receive antibiotic therapy when incision cannot be performed or in addition to incision. However, antibiotic concentrations in human abscesses are widely unknown. Pharmacokinetics of cefpirome in 12 human abscesses located in different body regions was studied. Cefpirome (2g) was administered as an intravenous short infusion, and concentrations were measured in plasma over an 8-h period and in abscesses at incision. A pharmacokinetic two-stage model was applied. At abscess incision performed 158 ± 112min after the start of the infusion, the cefpirome concentrations in the abscess fluid varied markedly, ranging from ≤0.1 (limit of quantification) to 47 (mean 8.4 ± 14.1) mg/L. Cefpirome was detectable in nine of 12 abscesses. Maximum concentrations were calculated to be 183 ± 106mg/L in plasma and 12 ± 16mg/L in the abscess. A cefpirome concentration of 2mg/L, which is the minimum concentration inhibiting growth of 90% of the most relevant bacterial pathogens, was exceeded spontaneously in six of 12 abscesses after a single dose. Cefpirome concentrations in the abscess did not correlate with either the pH or the ratio of surface area to volume of the abscesses, nor with plasma pharmacokinetics. Cefpirome may be useful to treat abscess patients because it was detectable in most abscesses after a single dose. However, the penetration of cefpirome into abscesses is extremely variable and cannot be predicted by measuring other available covariates.

Low cefpirome levels during twice daily dosing in critically ill septic patients: pharmacokinetic modelling calls for more frequent dosing.

To measure plasma levels and pharmacokinetics of cefpirome in critically ill septic patients with normal renal function. To use the pharmacokinetic model to simulate alternate dosing regimens and identify those that predict sustained levels. A prospective, open-label, descriptive study in a 22-bed, multidisciplinary, adult ICU in a university-affiliated, tertiary referral hospital. Twelve adults with normal renal function on enrollment and with suspected or documented sepsis in whom cefpirome was judged to be the appropriate therapy by the managing clinician. Cefpirome 2 g was infused intravenously over 3 min every 12 h. Timed blood samples were taken prior to and during two dosing intervals. Urine was collected for creatinine clearance determination. Two patients were non-evaluable due to renal dysfunction post-enrollment. The median cefpirome trough level was 1.1 mg/l (range 0.5-8.1 mg/l) after the initial dose and 1.4 mg/l (range < 0.5-15.9 mg/l) at 'steady state'. The volumes of distribution and elimination half-lives were greater and more variable than in healthy volunteers. Pharmacokinetic simulation predicted that more frequent bolus dosing, increased doses and continuous infusions would result in concentrations greater than 4 mg/l for over 60% of the dosing interval for all patients. Cefpirome 2 g twice daily produced low plasma troughs in a number of patients. Our data suggest that this drug regimen may be inadequate for successful treatment of difficult-to-treat infections in critically ill patients with normal renal function.

Pharmacokinetics of cefpirome during continuous venovenous hemofiltration: rationale for an 8-hour dosing interval.

Cefpirome is a new semisynthetic cephalosporin, primarily eliminated by the kidneys, that requires dosage adjustment in patients with kidney failure. The optimal dosing regimen of cefpirome in patients with continuous veno-venous hemofiltration (CVVH) is unknown. Pharmacokinetic properties of cefpirome were investigated in eight anuric patients with acute kidney failure treated by CVVH. All patients received a dosage of 2 g cefpirome every 8 hours after starting the hemofiltration with high-flux polysulfone membranes. Concentrations of cefpirome in plasma and ultrafiltrate were measured by HPLC. Total clearance and hemofiltration clearance of cefpirome were 589.1 +/- 164.5 mL/min and 43.3 +/- 7.8 mL/min, respectively. Serum elimination half-life was 2.36 +/- 0.59 hours. The highest plasma drug concentration was 14.8 +/- 3.2 microg/mL, and it declined to trough levels of 3.1 +/- 0.8 microg/mL at the end of the dosing interval. On the basis of previously published pharmacodynamic characteristics of cefpirome and the pharmacokinetic parameters obtained in this study, we calculated a required total daily dose of 2 g every 8 hours to achieve sufficient plasma antibiotic levels to cover the majority of target pathogens. However, this dosage may be insufficient during CVVH for intermediate resistant strains of Pseudomonas aeruginosa.

Pharmacokinetics of cefpirome in critically ill patients with renal failure treated by continuous veno-venous hemofiltration

To study the cefpirome pharmacokinetics of patients with sepsis and multiple organ failure treated with CVVH. Measurements of serum and ultrafiltrate (UF) concentrations and in vitro sensitivity testing of isolated micro-organisms. University hospital-based, single ICU. Six critically ill CVVH-dependent patients with sepsis and multiple organ dysfunction syndrome in need of antimicrobial therapy. Age range: 60-75 years; APACHE II score for severity of illness on admission: 19-30. One patient survived. Cefpirome i.v. was started at 2 g in 30 min, then continued 1 g i.v.b.i.d. The UF rate was 27 +/- 7 ml/min on day 1 and 34 +/- 2 ml/min on day 2. Serum and ultrafiltrate samples were measured by a validated high performance liquid chromatography assay. Volume of distribution: 23 x 5(SD +/- 4 x 6) l. Total cefpirome clearance was 32 +/- 6 x 3 ml/min; cefpirome CVVH clearance (ClCVVH): 17 +/- 4.2 ml/min; mean serum half-life (t1/2): 8.8 +/- 2.3 h; mass transfer on day 1: 660 +/- 123 mg/12 h (33 +/- 6% of administered dose) and day 2: 642 +/- 66 mg/12 h (64 +/- 7%). Estimated sieving coefficient (ClCVVH/UF rate): 64 +/- 11%. In vitro sensitivity of isolated microbes was excellent except for two non-sensitive enterococci and Candida spp. The sieving coefficient (64%) indicates that a substantial fraction of the drug is not filtered; clearance by pathways other than CVVH mounted to 50% of the total clearance and increased on day 2, indicating that the dosing schedule used is appropriate for this setting. Cefpirome appeared to be safe in these patients and effective for most of the nosocomial microbial isolates. During more than 90% of the time, serum levels were maintained above killing concentrations for susceptible micro-organisms.

Pharmacokinetics of cefpirome during the posttraumatic systemic inflammatory response syndrome.

To determine the pharmacokinetic parameters of cefpirome, a new so-called fourth-generation cephalosporin, in previously healthy trauma patients with posttraumatic systemic inflammatory response syndrome (SIRS) and to compare them to parameters obtained in matched, healthy volunteers. A prospective study. 12-bed surgical intensive care unit in a university hospital. 9 severe [Injury Severity Score, median (range) 29 (16-50)] trauma patients on mechanical ventilation with proven or suspected cefpirome-susceptible nosocomial infection, with no renal or hepatic failure, and healthy volunteers matched for age (+/- 5 years), sex, and body surface area (+/- 10%) were enrolled. All were men. Cefpirome (2 g twice daily) was continuously infused over a 0.5 h period alone or concomitantly with ciprofloxacin (400 mg over 1 h, twice daily). Antibiotic concentrations in plasma were measured by high-performance liquid chromatography; their pharmacokinetic parameters were evaluated at 12 time points after the first drug administration using a noncompartmental model. Cefpirome pharmacokinetic parameters for the two groups were similar despite a wider variation for trauma patients. Specifically, the median (range) time during which the cefpirome concentration in plasma remained over 4 mg/l (corresponding to the French lower cutoff determining cefpirome susceptibility) was 9.5 (7- > 12) and 9 (8-12) h for trauma patients and healthy volunteers, respectively. In the group of five patients receiving combined antibiotic therapy, the interindividual variability of pharmacokinetics was wider for ciprofloxacin than for cefpirome. No major pharmacokinetic modification was noted when cefpirome was given to trauma patients with posttraumatic SIRS without significant organ failure, indicating that no dosage adjustment seems required in this population. However, larger studies including determination of antibiotic levels in tissues are warranted to confirm these results.

高齢者におけるＣｅｆｐｉｒｏｍｅ（ＣＰＲ）の体内動態の検討

高齢者におけるＣｅｆｐｉｒｏｍｅ（ＣＰＲ）の体内動態の検討

Multiple-dose pharmacokinetics of cefpirome in long-term hemodialysis with high-flux membranes.

Cefpirome is a cephalosporin eliminated primarily by kidneys that requires dosage reduction in patients with renal failure. The pharmacokinetic parameters were studied in 10 patients with end-stage renal disease who were receiving hemodialysis. Repeated intravenous administration of 2 gm cefpirome three times a week resulted in trough levels of 12.2 +/- 5.4 micrograms/ml and peak serum concentrations of 99.6 +/- 82.1 micrograms/ml. After 3 1/2 hours of hemodialysis with polysulfone high-flux membranes, 62.3% +/- 23.3% of cefpirome was removed. The interdialytic half-life was 9.35 +/- 0.99 hours, and the intradialytic half-life was 2.02 +/- 0.7 hours.

Pharmacokinetics of cefpirome in pediatric patients.

Cefpirome is a new investigational cephalosporin. We designed a study to determine the pharmacokinetics and tolerance of cefpirome in pediatric patients. A single dose of cefpirome was administered intravenously over 15 min to 18 patients (age 0.5 to 18 years). The doses were 10 mg/kg of body weight for five patients, 25 mg/kg of body weight for seven patients, and 50 mg/kg of body weight for six patients. Blood samples were collected at 0, 0.25, 0.5, 1, 3, 5, and 8 h after the dose, and cefpirome was measured by a high-performance liquid chromatography method. The maximum concentration in serum ranged from about 53.6 to 454 micrograms/ml after doses of 10 to 50 mg/kg. The total body clearance, apparent volume of distribution, and elimination half-life were 2.15 +/- 0.70 ml/min/kg, 0.32 +/- 0.32 liter/kg, and 1.8 +/- 1.3 h, respectively. No significant adverse effects were attributed to cefpirome. These data may be useful in conducting efficacy and safety studies of cefpirome in pediatric patients.

Single-Dose Pharmacokinetics of Cefpirome in Paediatric Patients???

The disposition of cefpirome was evaluated in 37 children and adolescents with normal renal and hepatic function who were between 1 and 18.8 years of age, after a single intravenous dose of 10 mg/kg (n = 14; 9.2 ± 5.6 years), 25 mg/kg (n = 13; 8.5 ± 6.3 years) or 50 mg/kg (n = 10; 10.1 ± 4.9 years). The drug was quantified from plasma and urine by high-performance liquid chromatography from repeated samples obtained over a 24-hour postdose period. Evaluable data suitable for pharmacokinetic analysis were available for 33 of the study participants (10, 13 and 10 participants in the 10, 25 and 50 mg/kg dose groups, respectively). Mean plasma concentrations at 0.25 and 8.0 hours postdose for the 10, 25 and 50 mg/kg dose groups were 35.6/1.4, 105.4/2.8 and 208.6/4.8 mg/L, respectively. The mean area under the plasma concentration vs time curve (AUC0–∞) estimated by the linear trapezoidal rule for the 10, 25 and 50 mg/kg dose groups was 51.1, 177.2 and 339.7 mg/L·h, respectively. Pharmacokinetic parameters for cefpirome were determined using NONMEM, which revealed that a triexponential function best described the disposition profile. Population pharmacokinetic parameters (mean ± SEM) using this model were as follows: t1/2α= 0.3 ± 0.05h, t1/2β = 1.4 ± 0.2h, t1/2γ= 6.5 ± 1.7h, plasma clearance (CL) = 2.7 ±0.1 ml/min/kg (180.0 ± 9.9 ml/min) and apparent steady-state volume of distribution (Vdss) = 0.6 ± 0.1 L/kg. The mean (± SD) renal clearance (CLR) and fraction of cefpirome excreted unchanged in the urine were 1.3 ± 0.8 ml/min/kg and 44.1 ± 22.3%, respectively. When data from a study of cefpirome pharmacokinetics in adults were included with the subset of paediatric patients studied, a significant, nonlinear inverse correlation was found between age and both Vdss and CL. Pharmacokinetic parameters for cefpirome would support the use of a 25 or 50 mg/kg dose given at a 12-hour interval for infants and children of more than 1 year of age.

Single-dose pharmacokinetics of cefpirome in patients with renal impairment.

The pharmacokinetic parameters of cefpirome (HR 810) were examined in 22 patients with different degrees of renal impairment. HPLC was used to analyze samples of blood and urine for cefpirome; and enzymatic assay of creatinine in serum and urine was used to assess kidney function. Creatinine clearance correlated linearly with both total and renal clearance of cefpirome. The loss of kidney function resulted in a decreased renal clearance, whereas the volume of distribution remained the same. This result led to an increase in the terminal half-life of the drug, from 2 hours in healthy subjects to 14 1/2 hours in patients with uremia. This increase also resulted in a prolonged high serum concentration well above the minimum inhibitory concentration. The following dosages are thus recommended: (1) creatinine clearance greater than 50 ml/min: normal daily dose, (2) creatinine clearance from 20 to 50 ml/min: 50% of normal daily dose, and (3) creatinine clearance less than 20 ml/min: 25% of normal daily dose. An initial loading dose of 1 gm, independent of renal function, is advised. Cefpirome was safe and well tolerated.

腎機能障害者におけるcefpirome (CPR) の体内動態

The pharmacokinetics of cefpirome (CPR), a new injectable cephem, were studied in 9 patients with various degrees (classified by Ccr.) of impaired renal function. Serum and urinary concentrations of CPR were measured by bioassay. The pharmacokinetic analyses were based on a two compartment open model. As renal impairment increased, higher serum concentrations were maintained in beta-phase and higher urinary concentrations were kept over a long time, as well. As a conclusion, it is necessary to consider the adequate administration and dosage for patients with renal impairment to prevent side effects caused by the maintenance of cefpirome in serum over a long time.