scholarly journals Initial In Vivo Evaluation of a Novel Amikacin-Deoxycholate Hydrophobic Salt Delivers New Insights on Amikacin Partition in Blood and Tissues

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 85
Author(s):  
Styliani Xiroudaki ◽  
Federica Ianni ◽  
Samuele Sabbatini ◽  
Elena Roselletti ◽  
Claudia Monari ◽  
...  

In this study, an initial in vivo evaluation of a new amikacin-deoxycholate hydrophobic salt aimed at potentiating amikacin action against hard-to-treat lung infections was undertaken by quantifying, for the first time, amikacin in whole blood. Pharmacokinetic evaluation after intranasal administration in a murine model showed higher drug retention in the lungs compared to blood, with no significant differences between the salt and the free drug. Upon repeated administrations, the two treatments resulted in nonsignificant tissue damage and mild higher inflammation for the hydrophobic salt. Whole-blood analysis highlighted an unreported high partition of amikacin in blood components up to 48 h, while significant lung levels were measured up to 72 h. Such a new observation was considered responsible for the nearly overlapping pharmacokinetic profiles of the two treatments. To overcome such an issue, a dry powder in an inhalable form may be best suited. Moreover, if confirmed in humans, and considering the current once-a-day regimen for amikacin aerosols, important yet-to-be-explored clinical implications may be postulated for such amikacin persistence in the organism.

2014 ◽  
Vol 22 (10) ◽  
pp. 2733-2739 ◽  
Author(s):  
范建华 FAN Jian-hua ◽  
邓永波 DENG Yong-bo ◽  
宣明 XUAN Ming ◽  
周松 ZHOU Song ◽  
武俊峰 WU Jun-feng ◽  
...  

Bioanalysis ◽  
2019 ◽  
Vol 11 (19) ◽  
pp. 1737-1754 ◽  
Author(s):  
Paul Abu-Rabie ◽  
Bikalpa Neupane ◽  
Neil Spooner ◽  
James Rudge ◽  
Philip Denniff ◽  
...  

Aim: Collection and quantitative analysis in dry blood using volumetric absorptive microsampling (VAMS™) potentially offers significant advantages over conventional wet whole blood analysis. This manuscript explores their use for pediatric sampling and explores additional considerations for the validation of the bioanalytical method. Results: HPLC–MS/MS methods for the determination of midazolam and its major metabolite 1-OH midazolam in both whole wet blood, and dry blood collected on VAMS were developed, validated, and used to support an observational clinical study to compare pharmacokinetic parameters in pediatric patients. Conclusion: Validation data met internationally accepted guideline criteria. A strong correlation was observed in calculated concentrations between wet and dry test samples, indicating that VAMS is a suitable technique for use in pediatric clinical studies.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi34-vi34
Author(s):  
Georgios Batsios ◽  
Pavithra Viswanath ◽  
Peng Cao ◽  
Celine Taglang ◽  
Elavarasan Subramani ◽  
...  

Abstract The pentose phosphate pathway (PPP) generates NADPH and ribose 5-phosphate, which are involved in the scavenging of reactive oxygen species and the synthesis of nucleotides. As such, the PPP is typically upregulated in cancer cells to address the metabolic needs of rapid cell proliferation. Imaging PPP upregulation could therefore be useful in tumor assessment. One intermediate of the pathway is 6-phospho-δ-gluconolactone (6P-δ-GL), which is produced by phosphorylation of δ-gluconolactone. 6P-δ-GL is further metabolized to 6-phospho-gluconate (6PG). The goal of our study was to evaluate, for the first time, whether hyperpolarized (HP) δ-[1-13C]gluconolactone can be used to assess PPP flux and detect the presence of tumor in an orthotopic glioma rat model. Athymic nude rats bearing orthotropic U87 tumors or age-matched tumor-free controls were investigated. HP studies were performed following intravenous injection of HP δ-[1-13C]gluconolactone and metabolic images using a flyback spectral-spatial echo-planar spectroscopic imaging pulse were acquired. The data were processed using in-house Matlab code. 6P-δ-GL and 6-phospho-γ-[1-13C]gluconolactone were observed in all rats ~10 seconds after HP δ-[1-13C]gluconolactone injection, followed ~5 seconds later by production of 6PG observed at 179.3ppm. These data indicate that HP δ-[1-13C]gluconolactone likely crosses the blood-brain barrier, consistent with its transport via glucose transporters, and is rapidly metabolized. Importantly, 6PG was significantly higher in tumor voxels. The ratio of 6PG-to-6P-δ-GL was comparable in normal brain and in normal-appearing contralateral brain of tumor-bearing rats at 0.43±0.09 and 0.45±0.06 respectively (p=0.85), but significant higher in the tumor regions at 0.70±0.11 (p=0.04 and p=0.02 respectively), consistent with the elevated PPP flux that typically occurs in tumor cells. Our results indicate, to our knowledge for the first time, that metabolism of HP δ-[1-13C]gluconolactone can be assessed in the brain and that elevated 6PG production in glioma provides a potential metabolic imaging approach to probe tumor development, recurrence and response to therapy.


1976 ◽  
Vol 3 (2) ◽  
pp. 91-94 ◽  
Author(s):  
J. J. Malanify ◽  
C. E. Burns ◽  
D. A. Close ◽  
R. C. Bearse

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 946-946 ◽  
Author(s):  
Sherrill J. Slichter ◽  
Doug Bolgiano ◽  
Jill Corson ◽  
Mary Kay Jones ◽  
Todd Christoffel ◽  
...  

Abstract Background: With the introduction of bacterial testing, extended storage of platelets is now possible as long as platelet viability is maintained. Although apheresis platelets have recently been licensed for seven days of storage, platelet concentrates are still only licensed for five days. We performed studies to determine the post-storage viability of platelets stored as concentrates. As yet, there are no established criteria for platelet viability that must be met at the end of storage. However, two different criteria for evaluating post-storage platelet viability have been suggested: compare the stored platelet results with each donor’s fresh platelet results; or establish a fixed platelet standard with an expected mean value along with the lower limit of the 95% confidence interval (lower 95% CI) of the mean. Methods: Forty-four normal volunteers donated a unit of whole blood, the whole blood was centrifuged to give platelet-rich plasma (PRP), and the PRP was then centrifuged to produce a platelet concentrate. The platelet concentrates were re-suspended and stored in either 100% plasma or in 20% plasma and 80% Plasmalyte (a platelet storage solution) for five to eight days in Terumo Teruflex bags. At the end of storage, a sample of blood was obtained from each volunteer to prepare fresh platelets to compare the results of a fresh platelet transfusion with the transfusion of the same volunteer’s stored platelets. The fresh and stored platelets were alternately radiolabeled with either 51Cr or 111In, re-injected into their volunteer donor, and serial blood samples were drawn from the volunteer after transfusion of the fresh and stored platelets to determine platelet recoveries and survivals. Results: Results are shown in Table 1. Conclusions: After seven days of storage in plasma, the platelets could qualify for standards of: 74% and 53% as a simple ratio of fresh to stored platelet recoveries and survivals, respectively; according to Dumont’s method of analysis (Transfusion, in press), achievable stored platelet recoveries would be 63% of fresh and survivals would be 40% of fresh; and as a fixed standard, platelet recoveries averaged 45% and survivals 4.4 days with lower 95% CI’s of 35% and 3.3 days, respectively. After eight days of storage in plasma, platelet recoveries and survivals gave unacceptable results. Instead of increasing or at least maintaining post-storage platelet viability, Plasmalyte markedly reduced platelet viability compared to plasma stored platelets at each storage interval. In Vivo Radiolabeled Autologous Platelet Recoveries and Survivals STORAGE CONDITIONS PLATELET RECOVERIES (%) PLATELET SURVIVALS (Days) Solution Time (Days) N Fresh Stored Fresh Stored Data are given as the average ±1 S.D. Plasma 5 10 62±12 55±11 7.7±1.5 6.1±1.0 Plasma 6 10 61±7 46±12 8.2±1.5 5.1±1.6 Plasmalyte 6 3 47±30 29±16 5.1±3.4 1.8±0.2 Plasma 7 10 61±11 45±14 8.3±1.0 4.4±1.5 Plasmalyte 7 5 62±17 30±12 7.4±0.6 2.2±1.1 Plasma 8 3 67±12 31±8 8.3±0.6 2.9±0.8 Plasmalyte 8 3 70±3 21±8 8.2±0.8 0.7±0.1


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