Intravascular fibrinolysis in treating the thromboembolic changes in lower limbs

Introduction. One of the methods of treating the limbs ischaemia is local intravascular fibrinolysis. The aim of using this method is fast restoration of arteries patency what enables blood flow to the ischaemic limb and allows to diagnose the cause of the occlusion of arteries or a vascular bypass. Identification and determination of the changes type in the arterial wall allows to plan further treatment using surgical and endovascular methods. Material and methods. During 2003–2014, 41 patients were treated using the method of local fibrinolysis. In all of the cases the occlusion occurred in the femoropopliteal section. All of the patients had the colour Doppler echocardiography carried out, and then angiography, to confirm the diagnosis. The catheter was inserted through a puncture in the common femoral artery. The catheter tip was placed above the arterial thrombus. In 2003–2005 streptokinase was used as the fibrinolytic drug. Then, in 2005–2014 the usage of rtPA (alteplase) had been started. The progress of thrombolysis was monitored by repeated angiography. The fibrinolytic treatment had been continued for 6 more hours from obtaining the vessel patency confirmed by radiology. Results. In 15 patients (88%) in 2003–2005 (group in which streptokinase was used) and 21 patients (87.5%) in 2005–2014 (group in which alteplase was used) patency of the initially clotted artery and full remission of the ischaemic limb symptoms was obtained. In 4 cases the intravascular thrombolysis ended with failure. Simultaneously, embolectomy with Fogarty’s catheter was carried out. In the group treated with rtPA two deaths were noted: due to acute coronary syndrome and hypertensive crisis. Conclusions. Local intravascular fibrinolysis is a good and effective method of treatment of the limbs ischaemia in certain patients. It allows to lower the dosages of the thrombolytic drugs and can be a good alternative for the surgical treatment

Local intra-arterial thrombolysis for peripheral arterial occlusion

Wstęp: Jednym ze sposobów leczenia ostrego niedokrwienia kończyn jest wewnątrztętnicza fibrynoliza miejscowa. Celem jej stosowania jest szybkie przywrócenie drożności tętnicy, co umożliwia dopływ krwi do niedokrwionej kończyny i pozwoli rozpoznać przyczynę niedrożności tętnicy lub pomostu naczyniowego. Identyfikacja i określenie rodzaju zmian w ścianie tętnicy umożliwia zaplanowanie dalszego leczenia metodami operacyjnymi lub endowaskularnymi. Materiał i metody: Przez cały 2003 rok 5 chorych leczono metodą fibrynolizy miejscowej. We wszystkich przypadkach niedrożność dotyczyła odcinka udowo-podkolanowego. U wszystkich pacjentów wykonano badanie dopplerowskie kodowane kolorem, a następnie angiografię potwierdzającą rozpoznanie. Przez nakłucie tętnicy udowej wspólnej wprowadzano cewnik, którego koniec był umiejscowiony powyżej zakrzepu tętnicy. Jako lek fibrynolityczny stosowano streptokinazę. Postępy trombolizy monitorowano, powtarzając angiografię. Leczenie fibrynolityczne kontynuowano jeszcze przez 6 godzin od uzyskania radiologicznie potwierdzonej drożności naczynia. Wyniki: U wszystkich 5 leczonych uzyskano drożność pierwotnie zakrzepniętej tętnicy i pełną remisję objawów niedokrwienia kończyny. Wnioski: Wewnątrztętnicza fibrynoliza miejscowa jest dobrą i skuteczną metodą leczenia niedokrwienia kończyn u wybranych chorych. Pozwala na zmniejszenie dawki leków trombolitycznych i może być dobrą alternatywą dla leczenia operacyjnego.Background: Local intra-arterial thrombolysis is one of the methods of treatment of acute ischaemia of extremities. Its aim is the rapid restoration of arterial patency and the reperfusion of the ischaemic extremity. It also allows diagnosis of the cause of artery or graft occlusion. Identification and description of arterial wall lesions informs decisions optimizing further therapy, either surgical or endovascular. Material and methods: From January to December 2003, 5 patients with femoro-popliteal occlusions were treated with local intra-arterial thrombolysis. All patients underwent a colour Doppler examination followed by angiography, which confirmed the diagnosis. A catheter was introduced through a femoral artery puncture and its tip was localized in the region of the artery occlusion. All patients obtained streptokinase. The progress of thrombolysis was monitored by repeated angiography and treatment was continued for up to 6 hours after the radiographically confirmed restoration of patency of the vessel. Results: In all 5 treated patients we restored patency of the previously occluded artery and obtained complete remission of symptoms of lower limb ischaemia. Conclusions: Local intra-arterial thrombolysis is a safe and effective method of treating lower limb ischaemia in selected patients. It allows for a decrease in the total dose of the thrombolytic agent and can be a good alternative to surgical procedure

Determining the suitability of mass spectrometry for understanding the dissolution processes involved with pharmaceutical tablets

RATIONALE: A current challenge for analytical chemists is the development of measurement systems and approaches required to understand dynamic processes such as tablet dissolution. The design and development of oral tablets could be improved by the availability of detailed information about the rates of release of the individual tablet components. Small footprint mass spectrometry (MS) systems are gaining use for on-line reaction monitoring because of their ability to rapidly determine multiple reactant, intermediate, and product species. We have therefore assessed the utility of such MS systems to the study of dissolution processes. METHODS: Aqueous dissolution media containing phosphate and other non volatile buffer salts were pumped from a standard USPII dissolution vessel through an active splitter and back. The splitter sampled the dissolution stream and diluted it into a make-up flow which was pumped to a small single quadrupole mass spectrometer. Single ion monitoring was used to quantify the ions of interest. Three different bio-relevant dissolution media were studied to gauge the impact of the sample matrix. RESULTS: Individual dissolution profiles were obtained from a tablet containing three drugs and lactose as the soluble filler. This was successfully demonstrated with three different bio-relevant media designed to reflect the pH of the different sections of the human gastro-intestinal tract. Component concentrations as low as 0.06 μg/mL (representing 1% dissolution) were detected. The MS dissolution profiles correlated with the visual observation of tablet dissolution. MS gave linear responses with concentration for the individual components, although analysis of the tablet solution indicated that ion suppression is an area for further investigation CONCLUSIONS: An on-line MS system was used to determine the individual dissolution profiles of three drugs and lactose as they are released from the same tablet. The level of each of these components in solution was determined every 10 seconds, and each had a similar release profile. The dissolution profiles were determined using inorganic buffer solutions at three different bio-relevant pHs

The use of bile salt micelles for the prediction of human intestinal absorption

Human intestinal absorption (HIA) will dictate biopharmaceutical performance through its influence on absorption, distribution, metabolism, and elimination and can vary significantly depending upon the nature of the compound under consideration. In this study, an in vitro assay method is proposed for the prediction of HIA through the measurement of drug solubility in an aqueous phase containing micellar bile salt, namely sodium deoxycholate. A series of twenty compounds, displaying a range of physicochemical properties and known HIA values, were analyzed using UV spectroscopy to determine a solubilization ratio for each compound. A micelle/water partition coefficient (Kxm/a) was calculated and then used to develop an equation through simple linear regression; logit HIA = −0.919 + 0.4618 logKxm/a (R2 = 0.85). From this equation, a value for % HIA was determined which compared well with literature. Furthermore, 4 additional drugs were then analyzed using the developed equation and found to match well with literature, confirming the suitability of the method. Using a simple, economic, and robust UV bile salt assay allows prediction of HIA and avoids many of the disadvantages of other techniques, such as animal-based methods

Effects of medicines used to treat gastrointestinal diseases on the pharmacokinetics of coadministered drugs:A PEARRL Review

Background: Drugs used to treat gastrointestinal diseases (GI drugs) are widely used either as prescription or over23 the-counter (OTC) medications and belong to both the ten most prescribed and ten most sold OTC medications worldwide. Current clinical practice shows that in many cases, these drugs are administered concomitantly with other drug products. Due to their metabolic properties and mechanisms of action, the drugs used to treat gastrointestinal diseases can change the pharmacokinetics of some co27 administered drugs. In certain cases, these interactions can lead to failure of treatment or to the occurrence of serious adverse events. The mechanism of interaction depends highly on drug properties and differs among therapeutic categories. Understanding these interactions is essential to providing recommendations for optimal drug therapy. Objective: To discuss the most frequent interactions between GI and other drugs, including identification of the mechanisms behind these interactions, where possible. Conclusion: Interactions with GI drugs are numerous and can be highly significant clinically. Whilst alterations in bioavailability due to changes in solubility, dissolution rate and metabolic interactions can be (for the most part) easily identified, interactions that are mediated through other mechanisms, such as permeability or microbiota, are less well understood. Future work should focus on characterizing these aspects

The pig as a pre-clinical model for predicting oral bioavailability and in vivo performance of pharmaceutical oral dosage forms - a PEARRL review

Objectives: In pharmaceutical drug development, preclinical tests in animal models are essential to demonstrate whether the new drug is orally bioavailable and to gain a first insight into in vivo pharmacokinetic parameters that can subsequently be used to predict human values. Despite significant advances in the development of bio‐predictive in vitro models and increasing ethical expectations for reducing the number of animals used for research purposes, there is still a need for appropriately selected pre‐clinical in vivo testing to provide guidance on the decision to progress to testing in humans. The selection of the appropriate animal models is essential both to maximise the learning that can be obtained from such experiments and to avoid unnecessary testing in a range of species. Key findings: The present review, provides an insight into the suitability of the pig model for predicting oral bioavailability in humans, by comparing the conditions in the GIT. It also contains a comparison between the bioavailability of compounds dosed to both humans and pigs, to provide an insight into the relative correlation and examples on why a lack of correlation may be observed. Summary: While there is a general trend towards predicting human bioavailability from pig data, there is considerable variability in the data set, most likely reflecting species specific differences in individual drug metabolism. Nonetheless, the correlation between pigs vs. humans was comparable to that reported for dogs vs. humans. The presented data demonstrate the suitability of the pig as a preclinical model to predict bioavailability in human

Exploring gastrointestinal variables affecting drug and formulation behavior: methodologies, challenges and opportunities

Various gastrointestinal (GI) factors affect drug and formulation behavior after oral administration, including GI transfer, motility, pH and GI fluid volume and composition. An in-depth understanding of these physiological and anatomical variables is critical for a continued progress in oral drug development. In this review, different methodologies (invasive versus non-invasive) to explore the impact of physiological variables on formulation behavior in the human GI tract are presented, revealing their strengths and limitations. The techniques mentioned allow for an improved understanding of the role of following GI variables: gastric emptying (magnetic resonance imaging (MRI), scintigraphy, acetaminophen absorption technique, ultrasonography, breath test, intraluminal sampling and telemetry), motility (MRI, small intestinal/colonic manometry and telemetry), GI volume changes (MRI and ultrasonography), temperature (telemetry) and intraluminal pH (intraluminal sampling and telemetry)