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. 2016 Apr 5:2:9.
doi: 10.1186/s40780-016-0043-x. eCollection 2016.

Population pharmacokinetic analysis and dosing regimen optimization of penicillin G in patients with infective endocarditis

Toshiaki Komatsu  1 , Takayuki Inomata  2 , Ichiro Watanabe  2 , Masahiro Kobayashi  1 , Hideya Kokubun  1 , Junya Ako  2 , Koichiro Atsuda  1
Affiliations

Population pharmacokinetic analysis and dosing regimen optimization of penicillin G in patients with infective endocarditis

Toshiaki Komatsu et al. J Pharm Health Care Sci. .

Abstract

Background: This study was designed to evaluate the population pharmacokinetics (popPK) of penicillin G in patients with infective endocarditis and establish a dosage regimen based on pharmacokinetic data and clinical outcome.

Method: Forty-six serum penicillin G samples from 25 individuals were analyzed using a nonlinear mixed-effects model. popPK were estimated using a one-compartment model. We created a receiver operating characteristic (ROC) curve for penicillin G efficacy and the ratio of its minimum concentration (Cmin)/minimum inhibitory concentration (MIC). Simulations were used to optimize the penicillin G dosage regimen using this ratio.

Result: Estimated popPK were: CL (L/h) = 0.21 × creatinine clearance (CLcr) (mL/min), Vd (L) = 28.9. The areas under the ROC curves were 0.87 for clinical efficacy. The cut-off value of penicillin G Cmin/MIC was 60. The continuous administration of 1 million IU penicillin G/h was necessary to achieve a positive outcome for patients with normal renal function (CLcr ≥ 60 mL/min).

Conclusion: Our findings suggest that population-based parameters are useful for evaluating penicillin G pharmacokinetics and that an individualized dosage should be determined based on a described dosage regimen.

Keywords: Dosing optimization; Nonlinear mixed-effects model; Penicillin G; Population pharmacokinetics.

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Figures

Fig. 1
Fig. 1
Penicillin G minimum serum concentrations/MIC and logistic regression model for clinical outcomes (failure, 0; success, 1)
Fig. 2
Fig. 2
Receiver operating characteristic curve for predicting clinical efficacy using penicillin G minimum serum concentration/MIC
Fig. 3
Fig. 3
Relationship between observed penicillin serum concentrations (Cp) and predicted concentrations (PRED) (a), or individual predicted concentrations after Bayesian fitting (IPRED) (b). Scatter plot of conditional weighted residuals (CWRES) versus predicted PRED is presented in (c)
Fig. 4
Fig. 4
Probability of attaining targets above a penicillin minimum serum concentration/MIC ratio of 60 at CLcr ranging from 5 to 120 with MIC fixed at (a) 0.06 or (b) 0.12 μg/mL
Fig. 5
Fig. 5
Nomogram for the initial dosage of penicillin against viridans group streptococci
See this image and copyright information in PMC

References

    1. Tuğcu A, Yildirimtürk O, Baytaroğlu C, Kurtoğlu H, Köse O, Sener M, et al. Clinical spectrum, presentation, and risk factors for mortality in infective endocarditis: a review of 68 cases at a tertiary care center in Turkey. Turk Kardiyol Dern Ars. 2009;37:9–18. - PubMed
    1. Tawfiq JA, Sufi I. Infective endocarditis at a hospital in Saudi Arabia: epidemiology, bacterial pathogens and outcome. Ann Saudi Med. 2009;29:433–6. doi: 10.4103/0256-4947.57164. - DOI - PMC - PubMed
    1. Hoen B, Alla F, Selton-Suty C, Béguinot I, Bouvet A, Briançon S, et al. Changing profile of infective endocarditis: results of a 1-year survey in France. JAMA. 2002;288:75–81. doi: 10.1001/jama.288.1.75. - DOI - PubMed
    1. Habib G, Hoen B, Tornos P, Thuny F, Prendergast B, Vilacosta I, et al. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC) Eur Heart J. 2009;30:2369–413. doi: 10.1093/eurheartj/ehp285. - DOI - PubMed
    1. Craig WA. Pharmacokinetic pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998;26:1–10. doi: 10.1086/516284. - DOI - PubMed

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