Pharmacokinetics of sulbactam in humans

Foulds, George; Stankewich, J P; Marshall, Dennis C.; O’Brien, M. Margaret; Hayes, S.; Weidler, Donald J.; McMahon, Francis Gilbert

doi:10.1128/aac.23.5.692

Cited by 97 publications

(46 citation statements)

References 16 publications

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“…The ranges of plasma sulbactam concentrations we observed after iv infusion of 12.5-mg/kg doses are comparable to those reported for adult volunteers after 30-min iv infusion of 1,000 mg of sulbactam [9]. The mean apparent volume of distribution of 340 ml/kg estimated for previously healthy children also compares favorably with the mean value of 320 ml/kg for adult volunteers.…”

Section: Discussionsupporting

confidence: 72%

“…The mean apparent volume of distribution of 340 ml/kg estimated for previously healthy children also compares favorably with the mean value of 320 ml/kg for adult volunteers. However, the mean total plasma clearance rate of 180 ml/min per 1.73 m" in children is substantially lower than the mean value of "'240 ml/min per 1.73 m 2 in adults [9]. As a consequence, the mean terminal-phase halflife of 1.75 hr in children is significantly longer than the mean values of 0.97 and 0.99 hr reported for adult volunteers [9,10].…”

Section: Discussioncontrasting

confidence: 41%

“…The renal clearance accounts for "'77"10 of the total plasma clearance of sulbactam in children; a similar value has been reported for adults [9,10]. Thus, patients with renal dysfunction will require adequate dosage adjustments.…”

Section: Discussionmentioning

confidence: 59%

“…The recommended dosage for ampicillin is twice the sulbactam dosage. Studies of the co-administration of these compounds in adults have repeatedly shown that the two are compatible and synchronous in their pharmacokinetics [9,10].…”

Section: Schaad Guenin and Straehlmentioning

confidence: 99%

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Single-Dose Pharmacokinetics of Intravenous Sulbactam in Pediatric Patients

Schaad¹,

Guenin²,

Straehl³

1986

Clinical Infectious Diseases

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The pharmacokinetics of intravenously administered sulbactam were studied in 17 pediatric patients two to 14 years of age. Single doses of 12.5 or 25 mg/kg were infused over 3 min, and in previously healthy children, mean peak plasma concentrations 5 min after dosing were 71 and 163 ug/ml, respectively. Noncompartmental and compartmental calculations resulted in similar pharmacokinetic parameters. Linear pharmacokinetics were found in the concentration range studied. The mean terminal-phase half-life was 1.75hr, the mean total plasma clearance was 180 ml/min per 1.73 m-, and the mean apparent volume of distribution was 340 ml/kg. Approximately 70Ofo-80Ofo of an intravenous dose was excreted unchanged in the urine. In children with cystic fibrosis, both total plasma clearance and apparent volume of distribution were significantly increased. The data support the intravenous administration of 12.5-25 mg of sulbactam/kg every 6 to 8 hr for assessing the adequacy of this drug as an adjunct to 13-lactam therapy for various bacterial infections in children.An increasing number of gram-positive and gramnegative organisms that cause infections in children have become resistant to penicillin or cephalosporin compounds through the production of 13-lactamases, enzymes that destroy these antibiotics. One way of restoring the susceptibility of resistant strains of bacteria to these agents is by co-administering an inhibitor of 13-lactamases. Sulbactam is a potent and relatively stable 13-lactamase inhibitor that shows promise as an adjunct to 13-lactam therapy.The majority of the bacterial agents that cause respiratory tract infections (e.g., pneumonia, bronchitis, sinusitis, otitis), cellulitis, skeletal infections (e.g. arthritis, osteomyelitis), urinary tract infections, and meningitis in children are susceptible to sulbactam plus ampicillin. This group of pathogens includes the 13-lactamase-producing strains of Haemophi/us influenzae, Staphylococcus aureus, and Escherichia coli [1,2].In the present study we evaluated the pharmacoInformed consent for these studies was obtained from the parents of the study patients. The guidelines of the local Institutional Committee on Human Investigations were followed in the conduct of this research.

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Section: Discussionsupporting

confidence: 72%

Section: Discussioncontrasting

confidence: 41%

Section: Discussionmentioning

confidence: 59%

Section: Schaad Guenin and Straehlmentioning

confidence: 99%

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Single-Dose Pharmacokinetics of Intravenous Sulbactam in Pediatric Patients

Schaad¹,

Guenin²,

Straehl³

1986

Clinical Infectious Diseases

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“…2b). Mention must be made that sulbactam PK analysis was based on PK data of 12 h because of its very short half-life, i.e.,~1 h (18).…”

Section: Incorporation Of Covariatesmentioning

confidence: 99%

Population Pharmacokinetics of Fixed Dose Combination of Ceftriaxone and Sulbactam in Healthy and Infected Subjects

et al. 2015

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ABSTRACT. Increased antibacterial resistance (ABR) and limited drug discovery warrant optimized use of available antibiotics. One option is to rationally combine two antibiotics (fixed dose combination (FDC)) that may delay or prevent emergence of ABR in notorious pathogen. Major concern with FDC is the mutual interaction of its components that might influence their pharmacokinetic (PK) profile, requiring reassessing of whole formulation (adding cost and time). The interaction can be identified by comparing PK profile of a drug present in FDC with its independent entity. An open-label, crossover, single-dose comparative PK study of FDC (ceftriaxone and sulbactam) with their individual reference formulations was performed in 24 healthy adult subjects. No mutual PK interactions between ceftriaxone and sulbactam were observed. Pharmacokinetic data was used to develop a population-PK model to understand between-subject variability (BSV). Pharmacokinetics of ceftriaxone/sulbactam was explained by one and two compartment models, respectively. The subject's Bweight^was identified as a covariate explaining BSV. Both internal and external validations (healthy/infected subjects) were done. The modelderived population-PK parameters of FDC's active components in infected subjects were similar to literature reported values of individual components. Efficacies of various FDC dosage regimens over a range of minimum inhibitory concentrations (MICs) were assessed by Monte Carlo simulations using population-PK parameters of infected/healthy subjects. In infected subjects, 3 g FDC/24 h can treat bacteria with MIC ≤8 μg/mL, while for MIC 8-32 μg/mL, 3 g FDC/12 h is recommended. Lastly, the developed population-PK model was successfully used to predict drug exposure in pediatric population.

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