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Vivo Distribution (vivo + distribution)
Selected AbstractsIn Vivo Distribution of Liposome-Encapsulated Hemoglobin Determined by Positron Emission TomographyARTIFICIAL ORGANS, Issue 2 2009Takeo Urakami Abstract Positron emission tomography (PET) is a noninvasive imaging technology that enables the determination of biodistribution of positron emitter-labeled compounds. Lipidic nanoparticles are useful for drug delivery system (DDS), including the artificial oxygen carriers. However, there has been no appropriate method to label preformulated DDS drugs by positron emitters. We have developed a rapid and efficient labeling method for lipid nanoparticles and applied it to determine the movement of liposome-encapsulated hemoglobin (LEH). Distribution of LEH in the rat brain under ischemia was examined by a small animal PET with an enhanced resolution. While the blood flow was almost absent in the ischemic region observed by [15O]H2O imaging, distribution of 18F-labeled LEH in the region was gradually increased during 60-min dynamic PET scanning. The results suggest that LEH deliver oxygen even into the ischemic brain from the periphery toward the core of ischemia. The real-time observation of flow pattern, deposition, and excretion of LEH in the ischemic rodent brain was possible by the new methods of positron emitter labeling and PET system with a high resolution. [source] In vivo Distribution of Bismuth in the Mouse Brain: Influence of Long-Term Survival and Intracranial Placement on the Uptake and Transport of Bismuth in Neuronal TissueBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2005Agnete Larsen In medicine, bismuth-compounds have long been used to remedy gastrointestinal disorders; lately in combination with antibiotics to treat Helicobacter pylori associated peptic ulcers. An epidemic episode of bismuth-induced encephalopathy in France in the 1970s revealed the neurotoxic potential of bismuth. This incidence, involving almost 1000 patients, remains unexplained and the contribution of other factors besides bismuth has been postulated. Recently an autometallographic technique made it possible to detect bismuth in morphologically intact tissue. In the present study, autometallographicly detectable bismuth was seen throughout the brain following intraperitoneal and intracranial exposure. The neuronal staining pattern seems highly organized with some areas heavily stained and others with low or no staining. Long-term (8 months) intraperitoneal exposure led to higher bismuth uptake than short-term (2 weeks) exposure. Following both intraperitoneal and intracranial exposure, high amounts of bismuth were found in the reticular and hypothalamic nuclei, in the oculomotor and hypoglossal nuclei and in Purkinje cells. Within the central nervous system (CNS) retrograde axonal transport was seen after intracranial bismuth exposure. Axonal transport seems to influence the distribution of bismuth as the highest uptake of bismuth after intraperitoneal exposure was seen in the facial and the trigeminal motor nuclei, i.e. neurones with processes outside the blood-brain barrier, whereas these nuclei contained no bismuth following ic exposure. Ultrastructurally, accumulation of bismuth was seen in lysosomes. [source] A data base for partition of volatile organic compounds and drugs from blood/plasma/serum to brain, and an LFER analysis of the dataJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2006Michael H. Abraham Abstract Literature values of the in vivo distribution (BB) of drugs from blood, plasma, or serum to rat brain have been assembled for 207 compounds (233 data points). We find that data on in vivo distribution from blood, plasma, and serum to rat brain can all be combined. Application of our general linear free energy relationship (LFER) to the 207 compounds yields an equation in log BB, with R2,=,0.75 and a standard deviation, SD, of 0.33 log units. An equation for a training set predicts the test set of data with a standard deviation of 0.31 log units. We further find that the invivo data cannot simply be combined with in vitro data on volatile organic and inorganic compounds, because there is a systematic difference between the two sets of data. Use of an indicator variable allows the two sets to be combined, leading to a LFER equation for 302 compounds (328 data points) with R2,=,0.75 and SD,=,0.30 log units. A training equation was then used to predict a test set with SD,=,0.25 log units. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:2091,2100, 2006 [source] In vivo distribution and metabolisation of 14C-imidacloprid in different compartments of Apis mellifera LPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 11 2004Séverine Suchail Abstract In vivo distribution of the neonicotinoid insecticide, imidacloprid, was followed during 72 h in six biological compartments of Apis mellifera L: head, thorax, abdomen, haemolymph, midgut and rectum. Honeybees were treated orally with 100 µg of 14C-imidacloprid per kg of bee, a dose close to the median lethal dose. Elimination half-life of total radioactivity in honeybee was 25 h. Haemolymph was the compartment with the lowest and rectum that with the highest level of total radioactivity during the whole study, with a maximum 24 h after treatment. Elimination half-life of imidacloprid in whole honeybee was 5 h. Imidacloprid was readily distributed and metabolised only by Phase I enzymes into five metabolites: 4/5-hydroxy-imidacloprid, 4,5-dihydroxy-imidacloprid, 6-chloronicotinic acid, and olefin and urea derivatives. The guanidine derivative was not detected. The urea derivative and 6-chloronicotinic acid were the main metabolites and appeared particularly in midgut and rectum. The olefin derivative and 4/5-hydroxy-imidacloprid preferentially occurred in head, thorax and abdomen, which are nicotinic acetylcholine receptor-rich tissues. Moreover, they presented a peak value around 4 h after imidacloprid ingestion. These results explain the prolongation of imidacloprid action in bees, and particularly the differences between rapid intoxication symptoms and late mortality. Copyright © 2004 Society of Chemical Industry [source] Distribution of ifosfamide and metabolites between plasma and erythrocytesBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 3 2001T. Kerbusch Abstract The distribution of ifosfamide (IF) and its metabolites 2-dechloroethylifosfamide (2DCE), 3-dechloroethylifosfamide (3DCE), 4-hydroxyifosfamide (4OHIF) and ifosforamide mustard (IFM) between plasma and erythrocytes was examined in vitro and in vivo. In vitro distribution was investigated by incubating blood with various concentrations of IF and its metabolites. In vivo distribution of IF, 2DCE, 3DCE and 4OHIF was determined in 7 patients receiving 9 g/m2/72 h intravenous continuous IF infusion. In vitro distribution equilibrium between erythrocytes and plasma was obtained quickly after drug addition. Mean (±sem) in vitro and in vivo erythrocyte (e),plasma (p) partition coefficients (Pe/p) were 0.75±0.01 and 0.81±0.03, 0.62±0.09 and 0.73±0.05, 0.76±0.10 and 0.93±0.05 and 1.38±0.04 and 0.98±0.09 for IF, 2DCE, 3DCE and 4OHIF, respectively. These ratios were independent of concentration and unaltered with time. The ratios of the area under the erythrocyte and plasma concentration--time curves (AUCe/p) were 0.96±0.03, 0.87±0.07, 0.98±0.06 and 1.34±0.39, respectively. A time- and concentration-dependent distribution--equilibrium phenomenon was observed with the relative hydrophilic IFM. It is concluded that IF and metabolites rapidly reach distribution equilibrium between erythrocytes and plasma; the process is slower for IFM. Drug distribution to the erythrocyte fraction ranged from about 38% for 2DCE to 58% for 4OHIF, and was stable over a wide range of clinically relevant concentrations. A strong parallelism in the erythrocyte and plasma concentration profiles was observed for all compounds. Thus, pharmacokinetic assessment using only plasma sampling yields direct and accurate insights into the whole blood kinetics of IF and metabolites and may be used for pharmacokinetic,pharmacodynamic studies. Copyright © 2001 John Wiley & Sons, Ltd. [source] | |||||||||||||