Integration of pharmacokinetics and pharmacodynamics in antibiotic drug development and pharmacotherapy

Abstract

Abstract: Integration of pharmacokinetics (PK)/pharmacodynamics (PD)in antibiotic drug development allows the dosage regimen to be optimized, so that the desired effect can be achieved in a large proportion of the target patient population.In vitro kinetic and in vivo animal models have been extensively used in the evaluation of antibiotics.The value of these pre-clinical models in the PK and PD characterization of antibiotics is critically reviewed.A model based clinical development of antibiotics with integrating MIC distribution, PK parameter distribution, the PD target from animal models of infection, and the protein binding of the test drug, is also reviewed.

Key words: pharmacokinetics, pharmacodynamics, antibiotic, in vitro kinetic model, Monte Carlo simulation

CLC Number:

R969

SHI Jun. Integration of pharmacokinetics and pharmacodynamics in antibiotic drug development and pharmacotherapy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(2): 121-133.

References

[1] Drusano GL, Preston SL, Hardalo C, et al. Use of preclinical data for selection of a phase II III dose for evernimicin and identification of a preclinicalMIC breakpoint[J]. Antimicrob Agents Chemother, 2001;45:13-22.
[2] Ambrose PG, Bhavnani SM, Rubino CM, et al. Pharmacokinetics-pharmacodynamics of antimicrobial therapy:it' s not just for mice anymore[J]. Clin Infect Dis, 2007;44:79-86.
[3] Drusano GL.Antimicrobial pharmacodynamics:critical interactions of `bug and drug'[J]. Nat Rev Microbiol, 2004;2:289-300.
[4] Merrikin DJ, Briant J, Rolinson GN.Effect of protein binding on antibiotic activity in vivo[J]. J Antimicrob Chemother, 1983;11:233-238.
[5] Mueller M, de la Pena A, Derendorf H.Issues in pharmacokinetics and pharmacodynamics of anti-infective agents:kill curves versusMIC[J]. Antimicrob Agents Chemother, 2004;48:369-377.
[6] Cheung BW, Liu W, Ji P, et al. The chinchilla microdialy sis model for the study of antibiotic distribution to middle ear fluid[J]. AAPS J, 2006;8:E41-E47.
[7] Andes D, Craig WA.Animal model pharmacokinetics and pharmacodynamics: a critical review[J]. Int J Antimicrob Agents,2002;19:261-268.
[8] Andes D, Craig WA.Pharmacodynamics of the new fluoroquinolone gatifloxacin in murine thigh and lung infection models[J]. Antimicrob Agents Chemother, 2002;46:1665-1670.
[9] Andes D, Craig WA.Pharmacodynamics of a new streptogramin, XRP 2868, in murine thigh and lung infection models[J]. Antimicrob Agents Chemother, 2006;50:243-249.
[10] Andes D, Craig WA.In vivo activities of amoxicillin and amoxicillin-clavulanate against Streptococcus pneumoniae:application to breakpoint determinations[J]. Antimicrob Agents Chemother, 1998;42:2375-2379.
[11] Grasso S, Meinardi G, de Carneri I, et al. New in vitro model to study the effect of antibiotic concentration and rate of elimination on antibacterial activity[J]. Antimicrob Agents Chemother, 1978;13:570-576.
[12] Lowdin E, Odenholt I, Bengtsson S, et al. Pharmacodynamic effects of sub-MICs of benzylpenicillin against Streptococcus pyogenes in a newly developed in vitro kinetic model[J]. Antimicrob Agents Chemother, 1996;40:2478-2482.
[13] Lister PD, Pong A, Chartrand SA, et al. Rationale behind high-dose amoxicillin therapy for acute otitis media due to penicillin-nonsusceptible pneumococci:support from in vitro pharmacodynamics studies[J]. Antimicrob Agents Chemother, 1997;41:1926-1932.
[14] Lister PD, Wolter DJ, Wickman PA, et al. Levofloxacin imipenem prevents the emergence of high-level resistance among Pseudomonas aeruginosa strains already lacking susceptibility to one or both drugs[J]. J Antimicrob Chemother, 2006;57:999-1003.
[15] Lister PD.Pharmacodynamics of 750 mg and 500 mg doses of levofloxacin against ciprofloxacin-resistant strains of Streptococcus pneumoniae[J]. DiagnMicrobiol Infect Dis, 2002;44:43-49.
[16] Lister PD, Sanders CC.Pharmacodynamics of moxifloxacin, levofloxacin and sparfloxacin against Streptococcus pneumoniae[J]. J Antimicrob Chemother, 2001;47:811-818.
[17] Blaser J.Interactions of antimicrobial combinations in vitro:the relativity of synergism[J]. Scand J Infect Dis Suppl, 1990;74:71-79.
[18] Zinner SH, Dudley M, Blaser J.In vitro models for the study of combination antibiotic therapy in neutropenic patients[J]. Am J Med, 1986;80:156-160.
[19] Blaser J, Stone BB, GronerMC, et al. Impact of netilmicin regimens on the activities of ceftazidime-netilmicin combinations against Pseudomonas aeruginosa in an in vitro pharmacokinetic model[J]. Antimicrob Agents Chemother, 1985;28:64-68.
[20] Zinner SH, Blaser J, Stone BB, et al. Use of an in vitro kinetic model to study antibiotic combinations[J]. J Antimicrob Chemother, 1985;15:221-226.
[21] O' BrienM, Quach T, Gilbert D, et al. The antibacterial effects of ciprofloxacin and trovafloxacin against Streptococcus pneumonia in an in vitro dynamic model[J]. ClinMicrobiol Infect, 1999;5:12-15.
[22] Zinner SH, Gilbert D, Dudley MN.Activity of trovafloxacin (with or without ampicillin-sulbactam)against enterococci in an in vitro dynamic model of infection[J]. Antimicrob Agents Chemother, 1998;42:72-77.
[23] Craig WA, Ebert SC.Killing and regrowth of bacteria in vitro: a review[J]. Scand J Infect Dis Suppl, 1990;74:63-70.
[24] Fantin B, Leggett J, Ebert S, et al. Correlation between in vitro and in vivo activity of antimicrobial agents against gram-negative bacilli in a murine infection model[J]. Antimicrob Agents Chemother, 1991;35:1413-1422.
[25] Nolting A, Dalla Costa T, Rand KH, et al. Pharmacokineticpharmacodynamic modeling of the antibiotic effect of piperacillin in vitro[J]. Pharm Res, 1996;13:91-96.
[26] Zhi JG, Nightingale CH, Quintiliani R.Microbial pharmacodynamics of piperacillin in neutropenic mice of systematic infection due to Pseudomonas aeruginosa[J]. J Pharmacokinet Biopharm, 1988;16:355-375.
[27] Sheiner L, Wakefield J.Population modelling in drug development[J]. Stat MethodsMed Res, 1999;8:183-193.
[28] Sheiner LB, Ludden TM.Population pharmacokinetics dynamics[J]. Annu Rev Pharmacol Toxicol, 1992;32:185-209.
[29] Lomaestro BM, Drusano GL.Pharmacodynamic evaluation of extending the administration time of meropenem using a Monte Carlo simulation[J]. Antimicrob Agents Chemother, 2005;49:461-463.
[30] Breiman L, Friedman JH, Olshen R, et al. Classification and regression trees[M]. Belmont:Wadsworth Interanational Group, 1984.
[31] Shi J, Pfister M, Jenkins SG, et al. Pharmacodynamic analysis of the microbiological efficacy of telithromycin in patients with community-acquired pneumonia[J]. Clin Pharmacokinet, 2005; 44:317-329.