Impact of plasma protein binding on antimicrobial activity using time–killing curves

Zeitlinger, Markus; Sauermann, Robert; Traunmüller, Friederike; Georgopoulos, A.; Müller, Markus; Joukhadar, Christian

doi:10.1093/jac/dkh443

Cited by 86 publications

(96 citation statements)

References 16 publications

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“…Nilai ketersediaan hayati enrofloksasin pada anjing adalah 80% dan waktu paruh 4-5 jam (Plumb, 1999), namun persentase ikatan protein plasma pada beberapa spesies hewan lain bervariasi antara 15-40 % (Nites et al, 2011). Penelitian Zeitlinger et al (2004), menghasilkan penurunan efektivitas lebih dari 1 log 10 cfu/mL dengan penambahan albumin pada media agar untuk golongan flurokuinolon yaitu moksifloksasin. Menurut Uldemolins et al (2011), beberapa obat dengan nilai ikatan protein plasma 85-95% (ceftriaxone dan ertapenem) mengalami peningkatan nilai Vd dan Cl (klirens) hingga dua kali lipat pada penderita penyakit kritis disertai hipoalbuminemia.…”

Section: Pendahuluanunclassified

Hubungan Kadar Albumin dan Enrofloksasin dalam Plasma Anjing yang Diterapi Enrofloksasin

Wijayanti

Setiawan

2017

Acta Vet Indones

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ABSTRAKIkatan protein plasma terutama albumin dengan obat merupakan faktor penting yang harus dipertimbangan dalam terapi pada hewan. Hewan sakit umumnya mengalami hipoalbuminemia yang diakibatkan oleh kurangnya asupan nutrisi atau gangguan metabolisme protein pembentukan albumin akibat agen penyakit. Penelitian ini dilakukan untuk mengetahui hubungan kadar albumin pada pasien anjing yang sedang diterapi enrofloksasin dengan kadar enrofloksasin dalam plasma, untuk mengetahui seberapa besar persentase obat bebas yang memiliki nilai terapetik. Sampel darah diambil dari 10 pasien anjing dewasa berbagai ras satu jam setelah injeksi intra muskuler enrofloksasin dosis terapi (10 mg/kg berat badan) dan dimasukkan ke dalam tabung mengandung heparin. Sebagai pembanding juga dilakukan sampling darah terhadap 5 ekor anjing dewasa sehat berbagai ras untuk melihat kadar albumin dan kadar obat secara in vitro. Plasma diperoleh setelah proses sentrifugasi dan albumin diukur dengan metode bromcresolgreen serta kadar enrofloksasin diukur secara Kromatografi Cair Kinerja Tinggi. Hasil pengukuran kadar albumin menunjukkan perbedaan yang signifikan antara anjing sehat dan sakit yaitu 3,10 : 2,24 g/dL (P<0,05). Hasil pengukuran kadar enrofloksasin plasma anjing sakit menunjukkan rerata kadar 1,10 µg/mL, atau setara pada kadar albumin 1,7-2,6 g/dL pada uji kadar obat secara in vitro. Hasil ini menunjukkan bahwa semakin rendah kadar albumin maka kadar enrofloksasin yang terukur semakin tinggi, yang menunjukkan semakin rendah persentase ikatan albumin-obat.Kata kunci: anjing, ikatan albumin, enrofloksasin, kromatografi, plasma darah ABSTRACTThe plasma protein-drug mainly albumin binding plays an important role in therapy management of domestic animals. Many deseases generates the decrease of albumin that may caused by the lack of protein intake or the protein metabolism disorder. This research has deducted to study the correlation of albumin level and drug concentration in plasma of dog that received the enrofloxacin therapy to measure the percentage of free drug. The plasma were collected from 10 of mature sick dogs of various breeds an hour after injected therapeutic doses of enrofloxacin (10 g/kg) intramuscularly. Five healthy dogs were taken their blood to collect the plasma to measure the albumin and enrofloxacin level in vitro. Plasma collected after centrifugation, albumin and enrofloxacin levels were measured with bromcresol green and high performance liquid chromatography methods respectively. The results showed the significantly different of albumin levels beetwen healthy and sick dogs (3.10 : 2.24 g/dL, P<0.05). The enrofloxacin concentration measurement yielded the average of 1.10 µg/mL of sick dogs. This value was similar as value of enrofloxacin concentration of in vitro experiment at albumin level of 1.7-2.6 g/dL. It concluded that the lower of albumin level the higher enrofloxacin concentration of plasma, that it might explained the reducing of percentage the albumin-drug binding.

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Section: Pendahuluanunclassified

Hubungan Kadar Albumin dan Enrofloksasin dalam Plasma Anjing yang Diterapi Enrofloksasin

Wijayanti

Setiawan

2017

Acta Vet Indones

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“…However, in order to allow for predictions on the efficacy of an antibiotic in humans or animals, in vitro studies must be set out to acknowledge various aspects of in vivo conditions. PB is one of several factors which can substantially influence the PDs of an antibiotic (9,(46)(47)(48). Similar extents of PB have been shown to differentially affect the antimicrobial activity of highly protein-bound antibiotics (7,9,49,50) and impairment of antimicrobial activity in protein-rich medium may differ between gram-positive and gram-negative pathogens (9).…”

Section: Protein Binding In In Vitro Studies Of Antimicrobial Activitymentioning

confidence: 99%

“…Due to the absence of protein, in vitro PD studies using MHB as a test medium cannot usually account for the influence of PB on antimicrobial activity. Therefore, to investigate the impact of PB of bacterial killing of antibiotics, bacterial susceptibility is often determined in MHB and MICs are consecutively compared to those determined in a proteinrich medium (9,47,48). An alternatively used approach to assess the influence of PPB calculates the protein-free concentration of an antibiotic in serum or growth medium with addition of albumin and simulates antimicrobial activity of the total and the calculated free fraction in MHB (47).…”

Section: Protein Binding In In Vitro Studies Of Antimicrobial Activitymentioning

confidence: 99%

“…Alternatively to using serum, broth containing human albumin as a protein supplement is utilized (7,48). In this approach, concentrations of albumin usually around 5% are used, which widely excludes factors hampering bacterial growth (9).…”

Section: Mhbmentioning

confidence: 99%

“…Colony forming units per milliliter are plotted against time in the presence of different antibiotic concentrations (48,72,73). For the determination of the impact of PPB, bacterial counts at different time points are commonly obtained as follows: Culture tubes containing the medium and desired concentration of protein and antibiotic are kept in a water bath at 37°C to allow for PB to take place.…”

Section: Mhbmentioning

confidence: 99%

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Protein Binding of Antimicrobials: Methods for Quantification and for Investigation of its Impact on Bacterial Killing

Beer

Wagner

Zeitlinger

2009

AAPS J

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Abstract. Plasma protein binding of antimicrobial agents is considered to be a key characteristic of antibiotics as it affects both their pharmacokinetics and pharmacodynamics. However, up to the present, no standard methods for measuring protein binding or for quantification of the influence of protein binding on antimicrobial activity exist. This short-coming has previously led to conflicting results on antibacterial activity of highly protein-bound antibiotics. The present review, therefore, set out to summarize (1) methods for quantification of protein binding, (2) microbiological growth media used for determination of the impact of protein binding on antimicrobial activity of antibiotics, and (3) different pharmacodynamic in vitro studies that are used in this context. The advantages and disadvantages of a wide range of different approaches are discussed and compared. The urgent call for international standardization by microbiological societies and laboratories may be considered as a logical consequence of the presented data.

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Binding of licarbazepine enantiomers to mouse and human plasma proteins

Fortuna

Alves

Soares-da-Silva

2010

Biopharm & Drug Disp

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Racemic licarbazepine (Lic) is the active metabolite of oxcarbazepine (OXC) and eslicarbazepine acetate (ESL), appearing in human plasma as S-licarbazepine (S-Lic) and R-licarbazepine (R-Lic). However, human metabolism of OXC and ESL to Lic differs in the S-Lic/R-Lic enantiomeric ratio observed in plasma. S-Lic appears in higher proportion after ESL administration than after OXC (95% versus 80%). Enantioselective pharmacokinetics of Lic enantiomers have been found in mice after their separate administration and in humans following OXC treatment. Since protein binding of drugs may be enantioselective and a determining factor of pharmacokinetics, the binding of S-Lic and R-Lic to mouse and human total plasma proteins and, specifically, to human serum albumin (HSA) and alpha(1)-acid glycoprotein (AGP) were herein investigated for the first time. Free and bound fractions of S-Lic and R-Lic were separated by ultrafiltration after previous in vitro incubation of spiked plasma samples and protein solutions with each enantiomer at 10, 25 and 50 microg/ml. The results revealed that the extent of binding of Lic enantiomers to total plasma proteins was 30% and independent of the drug concentration and species considered. The data also suggest that the binding of Lic enantiomers to HSA is greater than that to AGP. Moreover, absence of enantioselectivity in the binding of Lic enantiomers to mouse and human plasma proteins and to HSA and AGP is evident. In conclusion, these findings suggest that the enantioselectivity observed in vivo in the biodisposition of S-Lic and R-Lic is not dependent on their affinity to plasma proteins.

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Impact of plasma protein binding on antimicrobial activity using time–killing curves

Abstract: Our data confirm the view that albumin substantially impairs the antimicrobial activity of antibiotics including moxifloxacin, a member of the class of fluoroquinolones.

Cited by 86 publications

References 16 publications

Hubungan Kadar Albumin dan Enrofloksasin dalam Plasma Anjing yang Diterapi Enrofloksasin

Hubungan Kadar Albumin dan Enrofloksasin dalam Plasma Anjing yang Diterapi Enrofloksasin

Protein Binding of Antimicrobials: Methods for Quantification and for Investigation of its Impact on Bacterial Killing

Binding of licarbazepine enantiomers to mouse and human plasma proteins

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