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D H Klein

Publications and source records attributed to D H Klein.

17 recordsLinked to original sources
PubMed1996

Recent developments in pharmacokinetic modeling of perfluorocarbon emulsions.

Perfluorocarbon (PFC) emulsions are potential oxygen carriers. This study is to investigate pharmacokinetic compartment models and physiologically based models, which correlate the distribution of PFC emulsion in the blood, reticuloendothelial system (RES) tissues and non-RES tissues with the excretion data. The models are evaluated by nonlinear regression analysis (using PCNONLIN software) with expiration data from animal following an i.v. injection of a concentrated perflubron emulsion. One model with four compartments (representing PFC emulsion in blood, RES tissues, non-RES tissues, and PFC solubilized in blood) meets the mathematical and physical criteria. The physiological modeling provides insight of physiological mechanisms. The relationship between the compartment model parameters (rate constants) and physiological parameters (tissue volumes, flow rates, etc.) is presented. An advantage of physiological model is that prediction may be made in interspecies scaling. The above two kinds of modeling are useful in many applications, e.g. to describe and predict the time course of PFC disposition throughout the body.

Animals↗
PubMed1996

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PubMed1994

Influence of perflubron emulsion particle size on blood half-life and febrile response in rats.

Perfluorochemical (PFC) emulsions are particulate in nature and, as such, can cause delayed febrile reactions when injected intravenously. This study investigated the influence of emulsion particle size on intravascular retention and on body temperature changes in unrestrained conscious rats. Concentrated (60% to 90% w/v) emulsions based on perflubron (perfluorooctyl bromide [PFOB]) with mean particle sizes ranging from 0.05 microns to 0.63 microns were tested. Rats were fitted with a chronic jugular catheter and an abdominal body temperature telemetry unit. Fully recovered, conscious rats were monitored for 24 hours after infusion (dose = 2.7 g PFC/kg). Emulsion blood half-life (T1/2) was determined from blood perflubron levels measured by gas chromatography. Emulsions with a particle size of 0.2-0.3 microns caused fevers (6 to 8 hour duration) which peaked at 1-1.5 degrees C above normal (approximately 37.5 degrees C). Fevers could be blocked by i.v. treatment with either cyclooxygenase inhibitors (ibuprofen) or corticosteroids (dexamethasone). Both intensity and duration of the temperature response, quantified by area under the temperature curve, was decreased significantly for emulsions with a particle size < or = 0.12 micron. Blood T1/2 varied inversely with particle size, and was 3 to 4 fold longer for emulsions with a mean particle size < or = 0.2 micron. Thus, smaller emulsion particles more effectively evaded the reticuloendothelial system, which resulted in longer intravascular retention, less macrophage activity, and reduced febrile responses.

Animals↗
PubMed1992

Development of highly fluid, concentrated and stable fluorocarbon emulsions for diagnosis and therapy.

A challenging aim in developing injectable fluorocarbon emulsions is to combine good flow characteristics (especially at low shear rates) with the high fluorocarbon concentration required for high oxygen delivery or effective contrast in imaging, long shelf life, and biological acceptability. A good balance of these sometimes conflicting objectives has been achieved with 90% w/v concentrated emulsions of various fluorocarbons, including the radiopaque oxygen carrier perfluorooctylbromide (PFOB, perflubron). The sterile emulsions have viscosities of about 20 cPs at a shear rate of 1 sec-1; the viscosity decreases rapidly with fluorocarbon concentration, and at 60% w/v the viscosity is less than that of human blood. The emulsions are suitable for injection as prepared, and are stable unfrozen for over a year.

Blood Substitutes↗
PubMed1992

Particle size distribution of concentrated perfluorocarbon emulsions by sedimentation field flow fractionation.

Alliance Pharmaceutical Corp's concentrated perflubron (perfluorooctylbromide; PFOB) emulsions are being developed for several medical applications. Sedimentation Field-Flow Fractionation (SdFFF) can provide accurate particle size distribution data when properly calibrated for those emulsions. Since no suitable particle standards are available with the proper density (approximately 1.9 g/cc) and size range (diameter = 0.1-1.0 microns), calibration of the mass distribution was done by comparing the SdFFF detector signal with the actual mass of perflubron extracted from fractions eluted at successive time points and measured by GC. The calibrated mass distribution can then be used to calibrate other instruments such as the photosedimentation instruments used for routine quality assurance measurements.

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