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Effect of Micronization on the Extent of Drug Absorption from Suspensions in Humans
Oh, Doo-Man,Curl, Rane L.,Yong, Chul-Soon,Amidon, Gordon L. 영남대학교 약품개발연구소 1996 영남대학교 약품개발연구소 연구업적집 Vol.6 No.-
A microscopic mass balance approach has shown that the initial saturation (is), absorption number (An), dose number (Do), and dissolution number (Dn) are four fundamental dimensionless parameters that can be used to estimate the fraction dose absorbed (F) of suspensions of poorly soluble drugs in humans. The dissolution number of a drug increases with decreasing its particle size. The effect of micronization on F for suspensions was investigated in terms of Dn. About 90% of maximal F can be achieved at Dn?2. Increasing the solubility of a drug results in better oral absorption through increasing Dn and decreasing Do. The fractions dose absorbed of digoxin, griseofulvin, and benoxaprofen agree with predicted F values using estimated parameters. Drugs with low Do and low Dn can be more completely in addition to micronization. Solubility at the physiological pH should be used for the estimation of the fraction dose absorbed.
Tracing the lactate shuttle to the mitochondrial reticulum
Brooks George A.,Curl Casey C.,Leija Robert G.,Osmond Adam D.,Duong Justin J.,Arevalo Jose A. 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Isotope tracer infusion studies employing lactate, glucose, glycerol, and fatty acid isotope tracers were central to the deduction and demonstration of the Lactate Shuttle at the whole-body level. In concert with the ability to perform tissue metabolite concentration measurements, as well as determinations of unidirectional and net metabolite exchanges by means of arterial–venous difference (a-v) and blood flow measurements across tissue beds including skeletal muscle, the heart and the brain, lactate shuttling within organs and tissues was made evident. From an extensive body of work on men and women, resting or exercising, before or after endurance training, at sea level or high altitude, we now know that Organ–Organ, Cell–Cell, and Intracellular Lactate Shuttles operate continuously. By means of lactate shuttling, fuel-energy substrates can be exchanged between producer (driver) cells, such as those in skeletal muscle, and consumer (recipient) cells, such as those in the brain, heart, muscle, liver and kidneys. Within tissues, lactate can be exchanged between white and red fibers within a muscle bed and between astrocytes and neurons in the brain. Within cells, lactate can be exchanged between the cytosol and mitochondria and between the cytosol and peroxisomes. Lactate shuttling between driver and recipient cells depends on concentration gradients created by the mitochondrial respiratory apparatus in recipient cells for oxidative disposal of lactate.
Halberstadt, Craig R.,Palsson, Bernhanrd O.,Midgley, A.Rees,Curl, Rane L. The Korean Society for Biotechnology and Bioengine 2002 Biotechnology and Bioprocess Engineering Vol.7 No.3
This report describes the use of a transtubular bioreactor to study the relative effects of diffusion versus perfusion of medium on antibody production by a hybridoma cell line. The study was performed with a high-density cell culture maintained in a serum-free, low-protein medium for 77 days. It was determined that the reactor possessed a macro-mixing pattern residence time distribution similar to a continuous stirred tank reactor (CSTR), However, due to the arrangement of the medium lines in the reactor, the flow patterns for nutrient distribution consist of largely independent medium path lengths ranging from short to long. When operated with cyclic, reversing, transtubular medium flow, some regions of the reactor (with short residence times) are more accessible to medium than others (with long residence times). From this standpoint, the reactor can be divided into three regions: a captive volume, which consists of medium primarily delivered via diffusion; a lapped volume, which provides nutrients through unilateral convection; and a swept volume, which operates through bilateral convection. The relative sizes of these three volumes were modified experimentally by changing the period over which the direction of medium flow was reversed from 15 min (larger captive volume) to 9 h (larger swept volume). The results suggest that antibody concentration increases as the size of the diffusion-limited (captive) volume is increased to a maximum at around 30 min with a sharp decrease thereafter. As reflected by changes in measured consumption of glucose and production of lactate, no significant difference in cellular metabolism occurred as the reactor was moved between these different states. These results indicate that the mode of operation of the transtubular bioreactor may influence antibody productivity under serum-free, low-protein conditions with minimal effects on cellular metabolism.