Pharmacokinetics of β-Lactam Antibiotics: Clues from the Past To Help Discover Long-Acting Oral Drugs in the Future

Overview

Journal ACS Infect Dis

Specialties Infectious Diseases
Microbiology
Pharmacology

Date 2018 Aug 25

PMID 30141902

Citations 12

Authors

Paul W Smith

Fabio Zuccotto

Robert H Bates

Maria Santos Martinez-Martinez

Kevin D Read

Caroline Peet

Ola Epemolu

Affiliations

Soon will be listed here.

Abstract

β-Lactams represent perhaps the most important class of antibiotics yet discovered. However, despite many years of active research, none of the currently approved drugs in this class combine oral activity with long duration of action. Recent developments suggest that new β-lactam antibiotics with such a profile would have utility in the treatment of tuberculosis. Consequently, the historical β-lactam pharmacokinetic data have been compiled and analyzed to identify possible directions and drug discovery strategies aimed toward new β-lactam antibiotics with this profile.

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References

Kang H, Lee M . Approaches for predicting human pharmacokinetics using interspecies pharmacokinetic scaling. Arch Pharm Res. 2011; 34(11):1779-88. DOI: 10.1007/s12272-011-1101-4. View

Newstead S . Recent advances in understanding proton coupled peptide transport via the POT family. Curr Opin Struct Biol. 2016; 45:17-24. PMC: 5628733. DOI: 10.1016/j.sbi.2016.10.018. View

Ramon-Garcia S, Gonzalez Del Rio R, Villarejo A, Sweet G, Cunningham F, Barros D . Repurposing clinically approved cephalosporins for tuberculosis therapy. Sci Rep. 2016; 6:34293. PMC: 5039641. DOI: 10.1038/srep34293. View

Jarlier V, Gutmann L, Nikaido H . Interplay of cell wall barrier and beta-lactamase activity determines high resistance to beta-lactam antibiotics in Mycobacterium chelonae. Antimicrob Agents Chemother. 1991; 35(9):1937-9. PMC: 245299. DOI: 10.1128/AAC.35.9.1937. View

Dhar N, Dubee V, Ballell L, Cuinet G, Hugonnet J, Signorino-Gelo F . Rapid cytolysis of Mycobacterium tuberculosis by faropenem, an orally bioavailable β-lactam antibiotic. Antimicrob Agents Chemother. 2014; 59(2):1308-19. PMC: 4335862. DOI: 10.1128/AAC.03461-14. View

Honeybourne D . Antibiotic penetration into lung tissues. Thorax. 1994; 49(2):104-6. PMC: 474317. DOI: 10.1136/thx.49.2.104. View

Smith D, Beaumont K, Maurer T, Di L . Relevance of Half-Life in Drug Design. J Med Chem. 2017; 61(10):4273-4282. DOI: 10.1021/acs.jmedchem.7b00969. View

Hugonnet J, Tremblay L, Boshoff H, Barry 3rd C, Blanchard J . Meropenem-clavulanate is effective against extensively drug-resistant Mycobacterium tuberculosis. Science. 2009; 323(5918):1215-8. PMC: 2679150. DOI: 10.1126/science.1167498. View

Zeitlinger M, Derendorf H, Mouton J, Cars O, Craig W, Andes D . Protein binding: do we ever learn?. Antimicrob Agents Chemother. 2011; 55(7):3067-74. PMC: 3122431. DOI: 10.1128/AAC.01433-10. View

10.

Wang F, Cassidy C, Sacchettini J . Crystal structure and activity studies of the Mycobacterium tuberculosis beta-lactamase reveal its critical role in resistance to beta-lactam antibiotics. Antimicrob Agents Chemother. 2006; 50(8):2762-71. PMC: 1538687. DOI: 10.1128/AAC.00320-06. View

11.

Potel G, Chau N, Pangon B, Fantin B, Vallois J, Faurisson F . Single daily dosing of antibiotics: importance of in vitro killing rate, serum half-life, and protein binding. Antimicrob Agents Chemother. 1991; 35(10):2085-90. PMC: 245330. DOI: 10.1128/AAC.35.10.2085. View

12.

Sotgiu G, DAmbrosio L, Centis R, Tiberi S, Esposito S, Dore S . Carbapenems to Treat Multidrug and Extensively Drug-Resistant Tuberculosis: A Systematic Review. Int J Mol Sci. 2016; 17(3):373. PMC: 4813232. DOI: 10.3390/ijms17030373. View

13.

Keener A . Oldie but goodie: Repurposing penicillin for tuberculosis. Nat Med. 2014; 20(9):976-8. DOI: 10.1038/nm0914-976. View

14.

Bergan T . Pharmacokinetic properties of the cephalosporins. Drugs. 1987; 34 Suppl 2:89-104. DOI: 10.2165/00003495-198700342-00008. View

15.

Flores A, Parsons L, Pavelka M . Genetic analysis of the beta-lactamases of Mycobacterium tuberculosis and Mycobacterium smegmatis and susceptibility to beta-lactam antibiotics. Microbiology (Reading). 2005; 151(Pt 2):521-532. DOI: 10.1099/mic.0.27629-0. View

16.

SNYDER N, Tabas L, Berry D, Duckworth D, Spry D, Dantzig A . Structure-activity relationship of carbacephalosporins and cephalosporins: antibacterial activity and interaction with the intestinal proton-dependent dipeptide transport carrier of Caco-2 cells. Antimicrob Agents Chemother. 1997; 41(8):1649-57. PMC: 163979. DOI: 10.1128/AAC.41.8.1649. View

17.

Kardos N, Demain A . Penicillin: the medicine with the greatest impact on therapeutic outcomes. Appl Microbiol Biotechnol. 2011; 92(4):677-87. DOI: 10.1007/s00253-011-3587-6. View

18.

Caldwell G, Masucci J, Yan Z, Hageman W . Allometric scaling of pharmacokinetic parameters in drug discovery: can human CL, Vss and t1/2 be predicted from in-vivo rat data?. Eur J Drug Metab Pharmacokinet. 2004; 29(2):133-43. DOI: 10.1007/BF03190588. View

19.

King D, Sobhanifar S, Strynadka N . One ring to rule them all: Current trends in combating bacterial resistance to the β-lactams. Protein Sci. 2016; 25(4):787-803. PMC: 4941212. DOI: 10.1002/pro.2889. View

20.

Iseki K, Sugawara M, Sato K, Naasani I, Hayakawa T, Kobayashi M . Multiplicity of the H+-dependent transport mechanism of dipeptide and anionic beta-lactam antibiotic ceftibuten in rat intestinal brush-border membrane. J Pharmacol Exp Ther. 1999; 289(1):66-71. View