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Pharmacokinetics of two oral cyclosporin a formulations in clinically stable heart-transplant patients
No full textIn order to evaluate the pharmacokinetics of cyclosporine A comparing the traditional (CsA-SCG) with the microemulsion formulation (CsA-ME), 20 clinically stable heart-transplant patients were enrolled in the study. All patients were on a thrice-daily dosage regimen (mean single dose 1.14±0.4 mg kg-1 body weight) of CsA-SCG. The steady-state area under the concentration-time curve during a dosage interval was calculated during three sequential periods: (1) the first after the morning oral dose of CsA-SCG; (2) the second (8 days later) after 2 hours intravenous infusion of cyclosporine; (3) the third after the CsA-ME morning oral dose (30 days after the milligram-to-milligram dose conversion). After switching from standard formulation CsA-SCG to CsA-ME, significant changes were observed in Cmax/ss (732 ± 178 vs 935 ± 250 ng ml-1, P < 0.001) and tmax (2.63 ± 1.21 vs 1.36 ± 0.49 h, P < 0.001). The CsA-ME mean bioavailability was higher than CsA-SCG (75 ± 19 vs 66 ± 16%; P < 0.001). The main CsA pharmacokinetic parameters of both formulations in clinically stable heart-transplant patients presented evident differences from data obtained in other transplant-patient populations. © 2001 Academic Press
Which reliable pharmacodynamic breakpoint should be advised for ciprofloxacin monotherapy in the hospital setting? A TDM-based retrospective perspective
No full textObjectives: To define in critically ill patients receiving intravenous (iv) ciprofloxacin (200 mg or 400 mg twice daily) and undergoing routine therapeutic drug monitoring (TDM) the interindividual pharmacokinetic variability and the reliable pharmacodynamic breakpoint enabled by these fixed dosing regimens according to the PK/PD principles and to the pattern of susceptibility to this antibiotic. Methods: Ciprofloxacin plasma concentrations [trough (Cmin) and 30 min post-dose peak (Cmax) levels] were analysed by means of an HPLC method. Optimal pharmacodynamic exposure was assessed by estimating the theoretical pharmacodynamic breakpoints (PD BP) for either Cmax or AUC. Results: The final database included 177 sets of Cmin and Cmax performed in 89 patients (200 mg twice daily group, n = 68; 400 mg twice daily group, n = 21). A very wide interindividual scatter of results was observed for both the 200 mg group and the 400 mg group. Interestingly, for both groups only moderate log-linear relationships between estimated renal function (CLCR) on one hand and either Cmin (r2 = 0.08, 0.28) or estimated AUC24 (r2 = 0.10, 0.34) on the other hand were found. Median PD BP, respectively, in the 200 mg twice daily group and the 400 mg twice daily group, were 0.16 and 0.28 mg/L for Cmax, and 0.19 and 0.29 mg/L for AUC24. Conclusions: Lowering ciprofloxacin dosage in the presence of renal failure seems in most cases unnecessary, since drug accumulation occurred only in a few cases. Optimal pharmacodynamic exposure with fixed 200 or 400 mg twice daily regimens of ciprofloxacin may be ensured only against fully susceptible microorganisms with an MIC < 0.3 mg/L. This supports the use of higher dosages in critically ill hospitalized patients, whereas the wide unpredictable interindividual pharmacokinetic variability suggests the usefulness of TDM with the intent of optimizing efficacy with ciprofloxacin therapy. © 2006 Oxford University Press
Quality control of monocyte volume and distribution width parameters of the Beckman Coulter DxH series
No full textPharmacokinetic profile of two different administration schemes of teicoplanin. Single 400 mg intravenous dose vs double-refracted 200 mg intramuscular doses in healthy volunteers
No full textObjective: To evaluate the pharmacokinetic appropriateness of a possible switch in dosing schedule for outpatients after hospital discharge, i.e. the bioequivalence of a single 400 mg intravenous daily dose versus double-refracted 200 mg intramuscular doses. Subjects and Methods: This study was conducted in 10 normal healthy volunteers using a two-way randomised, open-label, two-period crossover design. Each subject received two different drug regimens of teicoplanin: a single 400 mg intravenous daily dose versus double daily refracted 200 mg intramuscular doses. Teicoplanin serum concentrations were analysed by means of a fluorescence polarisation immunoassay system in samples collected for up to 72 hours after each regimen. Pharmacokinetic evaluations were performed by means of a 3-compartment open model with first-order elimination using the WinNonlin pharmacokinetic software package. Results: Teicoplanin peak serum concentrations were 97.96 ± 23.49 mg/L, 3.47 ± 1.00 mg/L and 6.99 ± 1.52 mg/L after a single 400 mg intravenous dose, and after the first and second intramuscular administrations, respectively. The trough level at 24 hours (C24) was 4.55 ± 1.04 mg/L after the 400 mg intravenous dose, and 6.67 ± 1.75 mg/L after double 200 mg intramuscular doses. The ratio between C24 intramuscular and intravenous treatment was 1.46 ± 0.17. Total body exposure (AUC(O-∞)) was 474.22 ± 111.77 mg/L·h post-intravenous dose, and 424.84 ± 113.53 mg/L·h post-intramuscular doses. Intramuscular bioavailability suggested substantial bioequivalence with intravenous administration (89.58 ± 14.35%). Dose-normalised data indicated that the intersubject variability was mainly related to interindividual differences in bodyweight. Conclusion: These findings indicated that a total daily dosage of teicoplanin 400 mg administered in two refracted doses by the intramuscular route could produce steady-state trough levels that are even higher than those achievable after once-daily intravenous administration during maintenance treatment. Since the time during which the serum concentration persists above MIC is actually thought to be a possible major determinant for the outcome of treatment with glycopeptides, this intramuscular schedule could enhance the pharmacokinetic exposure to teicoplanin. Therefore, a timely conversion from intravenous to intramuscular therapy in outpatients at the moment of hospital discharge (changing therapy from 400 mg intravenously once daily to 200 mg intramuscularly twice daily) may be reliably proposed, allowing better compliance without reducing efficacy
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Daunorubicin and daunorubicinol tissue concentrations in gastric cancer patients after local administration of a liposomal preparation.Pharmacol Res. 2007 Oct;56(4):344-9.
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