A Phase 1 Study To Assess the Pharmacokinetics of Intravenous Plazomicin in Adult Subjects with Varying Degrees of Renal Function

Allison S Komirenko, Valerie Riddle, Jacqueline A Gibbons, Scott Van Wart, Julie D Seroogy, Allison S Komirenko, Valerie Riddle, Jacqueline A Gibbons, Scott Van Wart, Julie D Seroogy

Abstract

Plazomicin is an FDA-approved aminoglycoside for the treatment of complicated urinary tract infections. In this open-label study, 24 adults with normal renal function or mild, moderate, or severe renal impairment (n = 6 per group) received a single 7.5-mg/kg of body weight dose of plazomicin as a 30-min intravenous infusion. Total clearance declined with renal impairment, resulting in 1.98-fold and 4.42-fold higher plazomicin exposures, as measured by the area under the concentration-time curve from 0 h to infinity, in subjects with moderate and severe impairment, respectively, than in subjects with normal renal function. (This study has been registered at ClinicalTrials.gov under identifier NCT01462136.).

Keywords: aminoglycosides; antimicrobial agents; pharmacokinetics; renal impairment.

Copyright © 2018 Komirenko et al.

Figures

FIG 1
FIG 1
Semilog plot of the mean (SD) plazomicin plasma concentration-time profile by renal function group.

References

    1. Center for Disease Dynamics Economics & Policy (CDDEP). 2015. The state of the world’s antibiotics 2015. Center for Disease Dynamics Economics & Policy, Washington, DC: .
    1. U.S. Centers for Disease Control and Prevention. 2013. Antibiotic resistance threats in the United States, 2013. U.S. Centers for Disease Control and Prevention, Atlanta, GA: .
    1. European Centre for Disease Prevention and Control. 2016. Surveillance of antimicrobial resistance in Europe 2016: annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). European Centre for Disease Prevention and Control, Stockholm, Sweden: .
    1. Morrill HJ, Pogue JM, Kaye KS, LaPlante KL. 2015. Treatment options for carbapenem-resistant Enterobacteriaceae infections. Open Forum Infect Dis 2:ofv050. doi:10.1093/ofid/ofv050.
    1. World Health Organization. 2017. Global priority list of antibiotic-resistant bacteria to guide research, discovery and development of new antibiotics. World Health Organization, Geneva, Switzerland: .
    1. López-Diaz MD, Culebras E, Rodriguez-Avial I, Rios E, Vinuela-Prieto JM, Picazo JJ, Rodriguez-Avial C. 2017. Plazomicin activity against 346 extended-spectrum-β-lactamase/AmpC-producing Escherichia coli urinary isolates in relation to aminoglycoside-modifying enzymes. Antimicrob Agents Chemother 61:e02454-16. doi:10.1128/AAC.02454-16.
    1. Galani I, Souli M, Daikos GL, Chrysouli Z, Poulakou G, Psichogiou M, Panagea T, Argyropoulou A, Stefanou I, Plakias G, Giamarellou H, Petrikkos G. 2012. Activity of plazomicin (ACHN-490) against MDR clinical isolates of Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. from Athens, Greece. J Chemother 24:191–194. doi:10.1179/1973947812Y.0000000015.
    1. Zhang Y, Kashikar A, Bush K. 2017. In vitro activity of plazomicin against β-lactamase-producing carbapenem-resistant Enterobacteriaceae (CRE). J Antimicrob Chemother 72:2792–2795. doi:10.1093/jac/dkx261.
    1. Cox G, Ejim L, Stogios PJ, Koteva K, Bordeleau E, Evdokimova E, Sieron AO, Savchenko A, Serio AW, Krause KM, Wright GD. 2018. Plazomicin retains antibiotic activity against most aminoglycoside modifying enzymes. ACS Infect Dis 4:980–987. doi:10.1021/acsinfecdis.8b00001.
    1. Castanheira M, Davis AP, Mendes RE, Serio AW, Krause KM, Flamm RK. 2018. In vitro activity of plazomicin against Gram-negative and Gram-positive isolates collected from United States hospitals and comparative activity of aminoglycosides against carbapenem-resistant Enterobacteriaceae and isolates carrying carbapenemase genes. Antimicrob Agents Chemother 62:e00313-18. doi:10.1128/AAC.00313-18.
    1. Achaogen, Inc. 2018. Zemdri (plazomicin) injection, for intravenous use. Achaogen, Inc, South San Francisco, CA: .
    1. Cass RT, Brooks CD, Havrilla NA, Tack KJ, Borin MT, Young D, Bruss JB. 2011. Pharmacokinetics and safety of single and multiple doses of ACHN-490 injection administered intravenously in healthy subjects. Antimicrob Agents Chemother 55:5874–5880. doi:10.1128/AAC.00624-11.
    1. Seroogy J, Choi T, Gall J, Van Wart S. 2017. Pharmacokinetics (PK) of plazomicin in healthy adults, poster 206. ASM Microbe, 1 to 5 June 2017, New Orleans, LA.
    1. Choi T, Seroogy J, Sanghvi M, Dhuria S. 2018. Mass balance, metabolism, and excretion of [14C]-plazomicin in healthy human subjects, poster 1400. IDWeek, 3 to 7 October 2018, San Francisco, CA.
    1. Cockcroft DW, Gault MH. 1976. Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41. doi:10.1159/000180580.
    1. Nayak-Rao S. 2010. Aminoglycoside use in renal failure. Indian J Nephrol 20:121–124. doi:10.4103/0971-4065.70839.
    1. Zhanel GG, Lawson CD, Zelenitsky S, Findlay B, Schweizer F, Adam H, Walkty A, Rubinstein E, Gin AS, Hoban DJ, Lynch JP, Karlowsky JA. 2012. Comparison of the next-generation aminoglycoside plazomicin to gentamicin, tobramycin and amikacin. Expert Rev Anti Infect Ther 10:459–473. doi:10.1586/eri.12.25.
    1. Pai MP, Nafziger AN, Bertino JS Jr. 2011. Simplified estimation of aminoglycoside pharmacokinetics in underweight and obese adult patients. Antimicrob Agents Chemother 55:4006–4011. doi:10.1128/AAC.00174-11.
    1. Kirkpatrick CM, Duffull SB, Begg EJ. 1999. Pharmacokinetics of gentamicin in 957 patients with varying renal function dosed once daily. Br J Clin Pharmacol 47:637–643.
    1. Dager WE. 1994. Aminoglycoside pharmacokinetics: volume of distribution in specific adult patient subgroups. Ann Pharmacother 28:944–951. doi:10.1177/106002809402800719.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren