Variations in protein binding of drugs in plasma and serum.

Ohshima, Taeyuki; Hasegawa, Takaaki; Johno, Ikuo; Kitazawa, Shigeru

doi:10.1093/clinchem/35.8.1722

Cited by 19 publications

(6 citation statements)

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“…This is consistent with the finding that all three polyzwitterions have very low protein adhesion when exposed to fibrinogen solution (Table ): At these negative surface potentials, the also negatively charged protein fibrinogen will not gain sufficient adhesion energy to irreversibly attach to the hydrophilic polyzwitterion surfaces. Similarly low protein adhesion for polyzwitterions has been previously reported by other groups. , …”

Section: Resultssupporting

confidence: 88%

“…Protein adhered at pH <5 but not above, corresponding to a protonation of the carboxylate groupdescribed at low pH, which shifted the charge of the material to polycationic. 39 On the other hand, the protein adhesion of a poly(methacrylate)-based poly(sulfobetaine) was insensitive of pH. 42 Our data on PZI also shows a pH-dependency of protein adhesion, but a very different one.…”

Section: Acs Applied Bio Materialsmentioning

confidence: 63%

“…Similarly low protein adhesion for polyzwitterions has been previously reported by other groups. 35,39 Toxicological studies of PZI, SMAMP, and PSB have been previously reported. 21 The additional toxicity studies of PCB can be found in the Supporting Information of this paper (Figure S4: Alamar Blue toxicity test; Figure S5: optical micrographs of cell growth on PCB; Figure S6: live-dead staining; all experiments were performed with human keratinocytes).…”

Section: Acs Applied Bio Materialsmentioning

confidence: 99%

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Simultaneously Antimicrobial, Protein-Repellent, and Cell-Compatible Polyzwitterion Networks: More Insight on Bioactivity and Physical Properties

Kurowska¹,

Eickenscheidt²,

Al‐Ahmad

et al. 2018

ACS Appl. Bio Mater.

102

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A poly(oxanorbornene)-based polyzwitterion with primary ammonium and carboxylate groups (PZI) has been reported previously as the first simultaneously antimicrobial and protein-repellent polyzwitterion. Here, additional physical and biological properties of three poly(oxanorbornene)-based polyzwitterions with different functional groups (PZI, the polycarboxybetaine (PCB), and the polysulfobetaine (PSB)) are compared to understand the molecular origins of this unusual bioactivity. Additionally, the three polyzwitterions and the antimicrobial polycationic SMAMP are exposed to proteins, bacteria suspensions, human plasma, and serum. These interactions are investigated by surface plasmon resonance spectroscopy. In protein adhesion studies, neither fibrinogen nor lysozyme adhere irreversibly to PZI, yet reversible interaction with lysozyme is observed at pH 7 and 8. In the presence of bivalent cations, reversible fibrinogen adhesion is observed on PZI and PSB but not on PCB. This might explain why mammalian cells grow on PZI and PSB but not on PCB. PZI does not show human plasma adhesion, whereas PCB and PSB have 0.27 and 0.48 ng mm–2 adhered plasma and SMAMP even at 6.3 ng mm–2. Both PZI and SMAMP show strong serum adhesion, whereas no serum adhered to PCB and only a little adhered to PSB. This could be related to the pH difference between serum and plasma to which the pH-responsive primary ammonium groups are susceptible while the permanently charged NR4 + groups are unaffected. Both PZI and PCB showed no or only a little bacterial adhesion. PCB is also intrinsically antimicrobial against E. coli and S. aureus bacteria and thus is also simultaneously protein-repellent and antimicrobially active. Thus, although the carboxylate groups of PZI and PCB seem to be a prerequisite for the dual antimicrobial activity and protein-repellency, the pH responsiveness of the primary ammonium group seems to make the PZI molecule vulnerable for protein adhesion in fluids that are slightly out of the physiological range.

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Section: Resultssupporting

confidence: 88%

Section: Acs Applied Bio Materialsmentioning

confidence: 63%

Section: Acs Applied Bio Materialsmentioning

confidence: 99%

See 1 more Smart Citation

Simultaneously Antimicrobial, Protein-Repellent, and Cell-Compatible Polyzwitterion Networks: More Insight on Bioactivity and Physical Properties

Kurowska¹,

Eickenscheidt²,

Al‐Ahmad

et al. 2018

ACS Appl. Bio Mater.

102

View full text Add to dashboard Cite

show abstract

“…Various factors can alter binding, but those acting in-vivo (such as interactions with other drugs or with other endogenous compounds, or concentration-dependent binding type) can be ruled out in this study. Other possible factors are changes in temperature, pH of the medium, and structure of the proteins (Allison & Comstock 1988;Ohshima et al 1989;Ratnaraj et al 1990).…”

Section: Resultsmentioning

confidence: 99%

Is Precipitation with Sulphosalicylic Acid Valid for Obtaining Free Valproic Acid and Phenytoin?

Sánchez

García

Durán

et al. 1999

Pharmacy and Pharmacology Communications

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The aim of this study was to compare ultrafiltration with protein precipitation with sulphosalicylic acid in the separation of free and protein‐bound serum phenytoin and valproic acid. Blood samples from 49 epileptic patients chronically treated with phenytoin (27) and valproic acid (22) were assayed. Free phenytoin or valproic acid were determined by fluorescent polarization immunoanalysis. The results showed that the free serum concentrations obtained by protein precipitation (24.9 ± 8.3 and 2.55 ± 1.61 mg L−1 for valproic acid and diphenylhydantoin, respectively) were almost three‐fold those from ultrafiltration (7.5 ± 6.2 and 0.86 ± 0.6 mg L−1, respectively). Protein separation using sulphosalicylic acid is not a valid technique for obtaining the free serum concentration of phenytoin or valproic acid.

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“…The samples were collected in serum separator vacutainers and allowed to dot before centrifugation. Serum was used rather than plasma to avoid possible alterations in binding secondary to heparin (7). Measurements of total and free serum levels of VA were performed by an immunoenzymatic technique (EMIT).…”

Section: Subjects and Samplesmentioning

confidence: 99%

Plasma protein binding kinetics of valproic acid over a broad dosage range: therapeutic implications

et al. 1993

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The aim of the study was to characterize, from the relationship between total and free serum levels of valproic acid obtained over a broad dosage range (10-50 mg/kg), the parameters defining the in-vivo kinetic behaviour of the binding of valproic acid to plasma proteins, their pharmacokinetic and clinical repercussions, and their application to therapeutic drug monitoring (TDM). The study was performed in nine healthy adults (20-35 years) who were given doses of 1000 (group A), 2000 (group B) and 3000 mg (group C) of sodium valproate according to a compensated cross-over design, simultaneously determining the total and free serum levels of valproic acid over a 24-h period. The mean free fraction increases with dose, although this increase is only significant (P < 0.05) for the highest dose (3000 mg). The variation in the free fraction of valproic acid begins to become significant (P < 0.05) at a total drug concentration above 100 mg/l. The mean values of the dissociation constant (K) and binding sites (n) were 460 mumol/l and 1.79, respectively, showing a variability of 86.6 and 38.7%, respectively, and a residual variability of 13.0%. Significant differences (P < 0.05) were found for the total plasma clearance (Cl) but not for the intrinsic plasma clearance (Clu) values, despite their tendency to decrease with the dose. If TDM is to be used for valproic acid, it is the free serum levels that should be determined, especially if high doses are administered, because the total serum levels are not a true reflection of the free ones, as is the case of other anti-epileptic drugs.

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Variations in protein binding of drugs in plasma and serum.

Cited by 19 publications

References 0 publications

Simultaneously Antimicrobial, Protein-Repellent, and Cell-Compatible Polyzwitterion Networks: More Insight on Bioactivity and Physical Properties

Simultaneously Antimicrobial, Protein-Repellent, and Cell-Compatible Polyzwitterion Networks: More Insight on Bioactivity and Physical Properties

Is Precipitation with Sulphosalicylic Acid Valid for Obtaining Free Valproic Acid and Phenytoin?

Plasma protein binding kinetics of valproic acid over a broad dosage range: therapeutic implications

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