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Intravenous Bolus Injection (intravenous + bolus_injection)
Selected AbstractsA randomized, double-blind trial demonstrating bioequivalence of the current recombinant activated factor VII formulation and a new robust 25°C stable formulationHAEMOPHILIA, Issue 5 2007B. V. BYSTED Summary., Recombinant activated factor VIIa (rFVIIa) is a well-established treatment for bleeding episodes in patients with congenital or acquired haemophilia A or B with inhibitors to factors VIII and IX and patients with FVII deficiency. The aim of this trial was to demonstrate bioequivalence between the currently marketed (rFVIIa/NovoSeven®) and a new rFVIIa formulation (VII25) stable at up to 25°C. Furthermore, short-term safety and tolerability of VII25 and pharmacokinetics of both formulations were investigated. In this single-centre, randomized, double-blind, two-way cross-over trial, healthy male subjects received one intravenous bolus injection of rFVIIa and one of VII25, both at 90 ,g kg,1, in a randomized order 2,3 weeks apart. Mean VII25/rFVIIa ratio for area under the plasma activity-time curve from time 0 to last quantifiable activity (primary bioequivalence endpoint), was 0.93, 90% confidence interval (CI) (0.89,0.96), within the predefined bioequivalence range (0.80,1.25). Secondary pharmacokinetic parameters were comparable between formulations. No serious adverse events were observed. Six mild or moderate treatment-emergent adverse events were reported in five subjects. Coagulation-related parameter profiles were similar between rFVIIa and VII25. No clinically abnormal changes were observed for laboratory parameters and no subjects developed FVIIa antibodies. This trial demonstrated bioequivalence between the currently available rFVIIa and VII25 stable at up to 25°C. VII25's ,user-friendly' formulation removes the inconvenience of storing/transporting at 2,8°C, and as the drug substance is the same, the activity and safety established for rFVIIa is maintained. [source] Real-Time Contrast Imaging: A New Method to Monitor Capillary Recruitment in Human Forearm Skeletal MuscleMICROCIRCULATION, Issue 3 2008Alexandra H. Mulder ABSTRACT Objective: Muscle capillary perfusion can be measured by contrast-enhanced ultrasound. We examined whether a less time-consuming ultrasound technique, called "real-time imaging," could be used to measure capillary recruitment in human forearm skeletal muscle. Methods: We measured microvascular blood volume and microvascular flow velocity using bolus injections of contrast microbubbles after forearm muscle exercise and a two-hour infusion of insulin into the brachial artery (both associated with capillary recruitment) and after sodium nitroprusside infusion (no changes in flow distribution). Results: After an intravenous bolus injection of the contrast agent, the steady-state concentration of contrast agent in forearm muscle lasted long enough (approximately 190 seconds) for the duration of the measurements (which take 70,80 seconds), rendering the continuous infusion of microbubbles unnecessary. Microvascular blood-volume measurements showed a good short-time reproducibility and a good reproducibility after repositioning of the forearm. Reproducibility of microvascular flow velocity was too low. Exercise and insulin infusion both increased microvascular blood volume, consistent with capillary recruitment. Sodium nitroprusside had no effect. Conclusion: Real-time contrast imaging, after bolus injections of an ultrasound contrast agent, provides reliable information about capillary recruitment in human forearm skeletal muscle, and may offer a valuable tool in studying human (patho)physiology. [source] WST11, A Novel Water-soluble Bacteriochlorophyll Derivative; Cellular Uptake, Pharmacokinetics, Biodistribution and Vascular-targeted Photodynamic Activity Using Melanoma Tumors as a Model,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2005Ohad Mazor ABSTRACT WST11 is a novel negatively charged water-soluble palladiumbacteriochlorophyll derivative that was developed for vascular-targeted photodynamic therapy (VTP) in our laboratory. The in vitro results suggest that WST11 cellular uptake, clearance and phototoxicity are mediated by serum albumin trafficking. In vivo, WST11 was found to clear rapidly from the circulation (t1/2= 1.65 min) after intravenous bolus injection in the mouse, whereas a longer clearance time (t1/2= 7.5 min) was noted in rats after 20 min of infusion. The biodistribution of WST11 in mouse tissues indicates hepatic clearance (t1/2= 20 min), with minor (kidney, lung and spleen) or no intermediary accumulation in other tissues. As soon as 1 h after injection, WST11 had nearly cleared from the body of the mouse, except for a temporal accumulation in the lungs from which it cleared within 40 min. On the basis of these results, we set the VTP protocol for a short illumination period (5 min), delivered immediately after WST11 injection. On subjecting M2R melanoma xenografts to WST11-VTP, we achieved 100% tumor flattening at all doses and a 70% cure with 9 mg/kg and a light exposure dose of 100 mW/cm2. These results provide direct evidence that WST11 is an effective agent for VTP and provide guidelines for further development of new candidates. [source] Cerebrospinal fluid concentrations of vincristine after bolus intravenous dosingCANCER, Issue 6 2002A surrogate marker of brain penetration Abstract BACKGROUND Vincristine (VCR) is used widely in oncology practice, and regular dosing is commonly associated with the development of sensorimotor or autonomic neuropathies. However, the incidence of VCR-related central nervous system (CNS) toxicity is comparatively low, suggesting that the blood-brain barrier may limit drug penetration into the brain parenchyma. This study determined whether measurable concentrations of VCR could be detected in the cerebrospinal fluid (CSF), as a surrogate marker of brain parenchyma penetration, after bolus intravenous injection in children without primary CNS pathology. METHODS The authors studied 17 pediatric patients ages 2.5,14.1 years (median, 6.8 years) with acute lymphoblastic leukemia or non-Hodgkin lymphoma without evidence of leptomeningeal disease. Patients received VCR 1.5 mg/m2 by intravenous bolus injection followed at varying intervals by lumbar puncture for scheduled intrathecal methotrexate administration under general anesthesia. Paired VCR concentrations in both plasma and CSF were measured in each patient simultaneously at times ranging from 8 minutes to 146 minutes after the VCR injection. Three patients were studied twice. The paired samples were stored at ,40 °C until analysis using a high performance liquid chromatography assay with a sensitivity of 0.1 ,g/L in CSF and 0.4 ,g/L in plasma. RESULTS Plasma VCR concentrations ranged from 2.2 ,g/L to 91.2 ,g/L. No measurable VCR concentrations were detected in the CSF samples. CONCLUSIONS Measurable concentrations of VCR in CSF are not achieved after the administration of standard intravenous bolus doses of VCR. The current observations are consistent with the relative rarity of VCR-related CNS neurotoxicity compared with the commonly observed sensorimotor and autonomic neuropathies. These findings suggest that the penetration of VCR into the brain parenchyma of patients with a relatively intact blood-brain barrier is low and that VCR may have a limited role in the CNS-directed therapy of these patients. Cancer 2002;94:1815,20. © 2002 American Cancer Society. DOI 10.1002/cncr.10397 [source] | ||||||||||