Possible Influence of Assay Methods in Studies of the Pharmacokinetics of Antibiotics

Pa, Miglioli; F, Pea; Mazzo, M; Berti, T; Lanzafame, Paola

doi:10.1080/1120009x.1993.11739205

Cited by 8 publications

(3 citation statements)

References 5 publications

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“…These are based on a microbiological assay [36], enzyme immunoassay [37], polarization fluoroimmunoassay [38], capillary electrophoresis [39], chemiluminescence (CL) [40], and chromatographic methods, which are the ones used in most pharmacopoeias [41,42]. The microbiological assay is inexpensive and simple, but its reproducibility is limited and it has a long incubation period.…”

Section: Quantitative Assay Of Gentamicin Sulfatementioning

confidence: 99%

Improvement of gentamicin poly(d,l-lactic-co-glycolic acid) microspheres for treatment of osteomyelitis induced by orthopedic procedures

et al. 2007

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Section: Quantitative Assay Of Gentamicin Sulfatementioning

confidence: 99%

Improvement of gentamicin poly(d,l-lactic-co-glycolic acid) microspheres for treatment of osteomyelitis induced by orthopedic procedures

et al. 2007

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“…Monitoring of blood drug concentrations thus plays an important role in achieving the maximum therapeutic outcome along with avoiding adverse events in pharmacotherapy, while fundamental pharmacokinetic and toxicokinetic examinations using experimental animals also contribute useful information for the assessment of pharmacological and toxicological responses to administered drugs. Although the measurement of drug concentrations in blood obtained from experimental animals has been performed using EMIT in several studies, [5][6][7] the reliability of measured values has not been fully examined despite the use of blood samples from sources other than human origin.…”

Section: Introductionmentioning

confidence: 99%

Underestimation of rat serum vancomycin concentrations measured by an enzyme‐multiplied immunoassay technique and the strategy for its avoidance

Konishi

Iga

Nagai

2013

Drug Testing and Analysis

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An enzyme-multiplied immunoassay technique (EMIT) has been widely adopted for the measurement of serum concentrations of vancomycin (VCM) in clinical practice. Because of the growing demand for its application to fundamental pharmacokinetic studies, we examined whether VCM concentrations in rat serum were accurately measured by EMIT. It was found that measured values of known amounts of VCM spiked to rat serum were markedly underestimated with a large analytical variance. When ultrafiltrated rat serum was used as the sample matrix, interference was significantly improved, and the degree of underestimation was attenuated also by diluting samples with physiological saline. These results suggest that endogenous substances of a high molecular weight in rat serum interfere with the analysis of VCM concentrations by EMIT. However, measured values of rat serum VCM concentrations by EMIT were restored to theoretical levels by exposing samples to 70°C for 3-7 min. A likely explanation for the avoidance of interference is that an appropriate thermal force eliminated the immunological function of endogenous substances falsely recognizing VCM without affecting the VCM molecule itself. Regarding serum samples collected from rats that were administered VCM, values measured by EMIT following the heat-treatment agreed well with those by the high performance liquid chromatography (HPLC) method. This is the first report showing interference by endogenous high-molecular substances in the measurement of drug concentrations in rat serum using EMIT. Our findings will contribute to the appropriate use of VCM based on evidence provided by clinical-oriented rat experiments requiring the measurement of serum VCM concentrations by EMIT.

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“…In the last three decades scientists have used a variety of techniques to measure the amount of gentamicin release and the release rate from different kinds of bone cements. These methods include fluorescence polarization immunoassay (FPIA),4, 5 enzyme‐linked immunosorbent assay (ELISA, dot‐ELISA),6 enzyme‐multiplied immunoassay technique (EMIT),7, 8 microbiological assay,9, 10 high performance liquid chromatography with fluorescence detection,11 and spectrophotometric methods 11–13. Radioenzymatic methods (ELISA, EMIT) and radioimmunoassays (FPIA) are reliable but very expensive, whereas chromatographic methods are time consuming 14.…”

Section: Introductionmentioning

confidence: 99%

Gentamicin release from two‐solution and powder–liquid poly(methyl methacrylate)‐based bone cements by using novel pH method

Merkhan

Hasenwinkel

Gilbert

2004

J Biomedical Materials Res

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The release of gentamicin as a function of time was measured for Palacos and two-solution bone cements by using a novel pH technique. The pH of an aqueous solution of gentamicin is a function of the gentamicin concentration and it decreases linearly over concentrations of 0.0-0.1 wt %. Therefore, a new, direct, and inexpensive in vitro technique was developed based on continuous readings of the pH in phosphate-buffered saline (PBS) at 37 degrees C to determine the release kinetics of gentamicin from poly(methyl methacrylate) (PMMA)-based bone cement. In addition, this method was used to compare the release profiles of Palacos R-40 bone cement with a two-solution bone cement developed in our laboratory and loaded with two different concentrations of gentamicin sulfate. Finally, the pH-based method was used to track the elution of gentamicin in both mixed and static conditions to determine the effect of mixing on the diffusion of gentamicin out of the cement. It was found that Palacos R-40 released 4.95 +/- 0.22 wt % of its gentamicin after 24 h in PBS solution. This data compares favorably with previously reported values of gentamicin elution from Palacos R-40, which ranged from 3 to 8 wt % of the total amount of incorporated gentamicin, depending on the size and the surface area of the samples. The results show that Palacos samples released 4.84 +/- 0.27 mg after 24 h, a two-solution cement loaded with an equivalent concentration of gentamicin sulfate released 3.81 +/- 0.52 mg, and two-solution cement loaded with twice the concentration of Palacos released 5.53 +/- 0.26 mg of gentamicin. A higher percentage of release was recorded from Palacos than from the two-solution bone cement, and the effect of PBS mixing conditions on the release kinetics was only significant in the early stages of release and not at 24 h. It was concluded that monitoring the pH is an effective technique to measure gentamicin release from PMMA-based bone cements in PBS solution.

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Possible Influence of Assay Methods in Studies of the Pharmacokinetics of Antibiotics

Cited by 8 publications

References 5 publications

Improvement of gentamicin poly(d,l-lactic-co-glycolic acid) microspheres for treatment of osteomyelitis induced by orthopedic procedures

Improvement of gentamicin poly(d,l-lactic-co-glycolic acid) microspheres for treatment of osteomyelitis induced by orthopedic procedures

Underestimation of rat serum vancomycin concentrations measured by an enzyme‐multiplied immunoassay technique and the strategy for its avoidance

Gentamicin release from two‐solution and powder–liquid poly(methyl methacrylate)‐based bone cements by using novel pH method

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