Resampling methods in sparse sampling situations in preclinical pharmacokinetic studies.

Toxicokinetic studies often require destructive sampling and the determination of drug concentrations in the various organs. Classically, the corresponding information is summarized in one mean concentration-time profile, which is regarded as representative for the animal population. On the basis of a mean profile, only estimates of the secondary pharmacokinetic parameters (for example AUC, t1/2) but no variability measures may be obtained. In this paper two resampling techniques are contrasted to Bailer's approach. The results obtained show that the resampling techniques can be considered a reliable alternative to Bailer's approach for the estimation of the standard error of the AUC t(k)0 in the case of normally distributed concentration data. They can be extended to the estimation of a variety of other secondary pharmacokinetic parameters and their respective standard deviations. One disadvantage with Bailer's method is its restriction to linear functions of the concentrations. On the other hand, using the population approach, prior knowledge of the underlying pharmacokinetic model is necessary. The resampling techniques discussed here, the "pseudoprofile-based bootstrap" (PpbB) and the "pooled data bootstrap" (PDB), are noncompartmental approaches. They are applicable under nonnormal data constellations and permit the estimation of the usual secondary pharmacokinetic parameters along with their standard deviations, standard errors, and other statistical measures. To assess the accuracy, precision, and robustness of the resampling estimators, theoretical data from three different pharmacokinetic models with different add-on errors (up to 100% variability) were analyzed. Even for the data sets with high variability, the parameters calculated with resampling techniques differ not more than 10% from the true values. Thus, in the case of data that are not normally distributed or when additional secondary pharmacokinetic parameters and their variability are to be estimated, the resampling methods are powerful tools in the safety assessment in preclinical pharmacokinetics and in toxicokinetics where generally sparse data situations are given.

Evaluation of air-particle abrasion of Y-TZP with different particles using microstructural analysis.

BACKGROUND: This study evaluated the effect of air-particle abrasion with different particle sizes on the surface roughness and phase transformation of yttria-stabilized tetragonal zirconia ceramics (Y-TZP). METHODS: Eighty-four Y-TZP discs of 15 mm diameter and 1.0 mm thickness were fabricated. The samples were divided into four groups (n = 21): (1) air-particle abrasion with 30 µm CoJet sand blast coating agent (CoJet, 3M ESPE); (2) 50 µm Al2O3 particles; (3) 110 µm Al2O3 particles; and (4) 250 µm Al2O3 particles. Each group was further divided into three subgroups each (n = 7) and treated for 5 seconds, 15 seconds and 30 seconds. Mean surface roughness was determined using a profilometer. The surfaces were analysed with a scanning electron microscope. XRD analysis was employed and the relative amount of the monoclinic phase was calculated. The results were statistically analysed by two-way analysis of variance (ANOVA, p < 0.05). RESULTS: Air-particle abrasion with 250 µm Al2O3 particles for 30 seconds had the highest surface roughness (p < 0.001) and a significantly higher amount of monoclinic phase compared to air-particle abrasion with 30 µm, 50 µm and 110 µm particles (p < 0.001). CONCLUSIONS: Duration and particle size of air-particle abrasion affects the roughness and phase transformation of Y-TZP. Longer treatment times with larger particles may result in degradation of material.

Bioactivity and protein attachment onto bioactive glasses containing silver nanoparticles.

There is much interest in silver containing glasses for use in bone replacement owing to the demonstrated antibacterial effect. In this work, 2 and 8 mol % of silver was added during the sol-gel process to the composition of a bioactive glass belonging to CaO-SiO(2 -P(2)O(5) system. The samples were characterized by means of ultraviolet-visible spectroscopy and X-ray photoelectron spectroscopy (XPS) techniques to demonstrate that the silver is embedded into the glass matrix as nanoparticles. Bioactivity test in simulated body fluid proved that the presence of silver in the bioactive glass composition, even in high amount, preserve or even improve the bioactivity of the starting glass, and consequently, leads to the carbonated apatite formation, which is the prerequisite for bioactive materials to bond with living bones. Complementary information proving these findings were delivered by performing X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, energy dispersive spectroscopy, and XPS measurements. The presence of silver also improves protein binding capability to the bioactive glass surface as demonstrated by cw-electron paramagnetic resonance experiments and XPS measurements.

Bond-coating in plasma-sprayed calcium-phosphate coatings.

The influence of bond-coating on the mechanical properties of plasma-spray coatings of hydroxyatite on Ti was investigated. Plasma-spray powder was produced from human teeth enamel and dentine. Before processing the main apatite coating, a very thin layer of Al2O3/TiO2 was applied on super clean and roughened, by Al2O3 blasting, Ti surface as bond-coating. The experimental results showed that bond-coating caused significant increase of the mechanical properties of the coating layer: In the case of the enamel powder from 6.66 MPa of the simple coating to 9.71 MPa for the bond-coating and in the case of the dentine powder from 6.27 MPa to 7.84 MPa, respectively. Both tooth derived powders feature high thermal stability likely due to their relatively high content of fluorine. Therefore, F-rich apatites, such those investigated in this study, emerge themselves as superior candidate materials for calcium phosphate coatings of producing medical devices. The methods of apatite powder production and shaping optimization of powder particles are both key factors of a successful coating. The methods used in this study can be adopted as handy, inexpensive and reliable ways to produce high quality of powders for plasma spray purposes.

Analysis of pseudo-profiles in organ pharmacokinetics and toxicokinetics.

In general, the pharmacokinetic model parameters, like rate constants, area under the curve (AUC) etc. are estimated via a two-stage procedure, where the values obtained from concentration-time relationships within one subject (experimental unit) are considered to be functionally related to the drug concentrations measured. In many cases 'mean' estimators and their respective standard errors are calculated afterwards. The determination of drug concentrations in organs as well as in the serum of small animals (mice, rats) in dependence of the time after administration often does not permit the establishment of reasonable profiles within one subject suited for conventional pharmacokinetic analyses and tolerability studies. Frequently, only one experimental value per organ or animal is recorded. The consequence is that most pharmacokinetic parameters are to be estimated on the basis of the mean concentrations rather than via the mean of individual parameter estimates. In all cases of a non-linear relationship between a target item and the concentration, the mean-concentration based estimators and the two-stage profile based estimators need not coincide. In addition, in the former case variance estimators may be either difficult to obtain or not deducible. In order to get variance estimators as well as to enable comparisons between different treatment regimens, in addition to bioequivalence testing as a step towards human dose finding studies, various resampling techniques (parametric and non-parametric bootstrap) were applied to generate pseudo-profiles from independent measurements and compared to their more conventional counterparts where applicable. Simulation studies based on different predefined pharmacokinetic models (first-order elimination after i.v. bolus, first-order elimination after first-order absorption, simple capacity-limited kinetics) revealed that even the non-parametric pseudo-profile stratified 'bootstrap' (resampling with replacement per time point) performs quite satisfactorily.

Shear bond strength of resin luting cement to glass-infiltrated porous aluminum oxide cores.

STATEMENT OF PROBLEM: Resin bonding surface treatment methods for conventional silica-based dental ceramics are not reliable for glass infiltrated high alumina content In-Ceram ceramics. PURPOSE: This study developed an alternative surface treatment to improve resin bonding of glass-infiltrated aluminum oxide ceramic blasting with diamond particles and then observed the efficiency of this treatment. Material and methods. In-Ceram test specimens were prepared and divided into 2 groups. All specimens were sandblasted with Al(2)O(3), and blasted with diamond particles and 2 adhesive resins were applied. After bonding and storage in humid conditions, shear bond strength values were measured with a universal testing machine. Surface roughness and fracture interfaces were determined with a perthometer and a SEM. RESULTS: The highest bond strength was obtained on the samples blasted with diamond particles (group II). The differences between the 2 groups and the 2 adhesive resin cements were both statistically significant. CONCLUSION: Panavia-Ex cement exhibited higher bond strength than Super-Bond cement. This higher bond strength was attributed to ceramic oxide and ester bond and the mechanical properties of Panavia-Ex cement.