Abstract
Avibactam, a potent non-β lactam β-lactamase inhibitor, was recently approved in the
USA for combination use with ceftazidime, a cephalosporin antibiotic drug. The addition
of avibactam potentiates the antimicrobial drug ceftazidime, which otherwise would
have been susceptible to β-lactamases produced by variety of Gram negative pathogens.
The focus of this review was to provide clinical pharmacokinetic data of avibactam
to cover absorption, distribution, metabolism, and excretion aspects including any
potential for avibactam to show drug-drug interactions in the clinic. Based on the
review of the data, the pharmacokinetics of avibactam was generally stationary in
the studied dosing regimen. The elimination half-life (approximately 1.4- 3.2 h) and
volume of distribution at steady state (15.4-26.3 L) were found similar across the
studies and therefore, provided the complementary pharmacokinetic attributes for combination
use with ceftazidime. Renal excretion was the major pathway for the clearance of avibactam.
In summary, any degree of renal dysfunction is expected to alter the pharmacokinetics
of avibactam – this consideration should be factored in dosage adjustments while dosing
in patients with renal impairment. Concomitant drugs that may influence renal mechanism
of elimination of avibactam should be avoided and/or monitored for any impact on the
pharmacokinetics of avibactam.
Key words
Avibactam - ceftazidime - β-lactamase - pharmacokinetics - pharmacodynamics - drug-drug
interaction
