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Biomedical subjects

P V Pedersen

Publications and source records attributed to P V Pedersen.

17 recordsLinked to original sources
PubMed1979

Congenital ascites due to mesenteric vessel constriction caused by malrotation of the intestines.

A newborn premature girl with congenital, non-chylous ascites is presented. The ascites recurred although laparocentesis was performed three times. The ascites was probably due to a superior mesenteric vein constriction caused by a malrotation of the intestines. After division of the Ladd-bands no ascites recurred. Non-chylous, congenital ascites may have a surgically treatable cause.

Ascites↗
PubMed1978

General treatment of linear pharmacokinetics.

A general treatment of linear pharmacokinetics that enables equations to be obtained simply for all linear compartmental models, with input in one or more compartments, is presented. Two approaches are described: one based on a full Laplace transformation and one that avoids transformation of the input functions and the use of convolution integrals. The latter approach is of particular interest when dealing with complex input functions not having a simple Laplace transform. The concept of acceptor and donor subsystems is introduced. It is demonstrated that disposition in certain models may be simplified and analyzed in terms of disposition in subsystems of simpler composition. The treatment presented is illustrated with several examples.

Kinetics↗
PubMed1978

General treatment of competitive binding of small molecules to macromolecules as applied to dynamic dialysis: theoretical analysis.

A mathematical analysis of the dynamic dialysis process is presented, demonstrating how the process can be applied generally to study competitive and noncompetitive binding between small molecules and macromolecules. A law of mass action model for competitive binding with independent sites and classes with equivalent sites (CIE) is considered as a specific case without loss of generality. The escape profiles of two compounds are calculated to illustrate the effect of an increasing degree of binding competition. Noisy data are generated using the CIE model to test the presented method of estimating competitive binding parameters. The parameters estimated by the nonlinear regression technique came close to the true values, considering the degree of noise added to the exact dialysis data. A transformation approach is presented, enabling initial estimates of the binding parameters in the CIE model to be determined by multiple linear regression, thereby eliminating the main problem in the nonlinear estimation. The presented method of analysis is extended to strongly bound compounds, which also bind significantly to the dialysis membrane.

Binding, Competitive↗
PubMed1978

Versatile kinetic-approach to analysis of dissolution data.

A new kinetically based dissolution equation is presented that considers dissolution of polydisperse systems and disintegrating solid dosage forms. The equation is applicable under sink as well as nonsink conditions and enables the specific dissolution rate parameter, the dispersion parameter, the disintegration lag time, and a newly introduced parameter, the dissolution availability, to be evaluated simultaneously and directly from percent of label claim dissolved versus time data. The equation showed excellent fit to dissolution data for aminophylline tablets. The kinetic significance of the estimated parameters of the equation is discussed. The method of analysis is compared to an approach employing an empirical equation based on a modified Weibull distribution function.

Aminophylline↗
PubMed1977

New method for characterizing dissolution properties of drug powders.

Various multiparticulate dissolution models that assume a log-normal particle-size distribution are fitted by nonlinear least-squares regression to data from the dissolution of micronized glyburide. Estimates of parameters describing the effective initial particle-size distribution are obtained, together with estimates of the specific dissolution rate parameter. A dissolution equation based on an ideal, untruncated, log-normal distribution, with the single particles dissolving according to the Hixson-Crowell cube root law, is the best model. The dissolution behavior of glyburide can be well described by this model in terms of the specific dissolution rate parameter and one other parameter accounting for the distribution effect. The estimation of these two parameters represents a more exact way of describing the dissolution characteristics of drug powders than previous approaches. The method should be of interest in the quality control of drugs that may cause bioavailability problems because of dissolution rate-limited absorption.

Chemistry, Pharmaceutical↗
PubMed1977

General class of multiparticulate dissolution models.

The dissolution of multiparticulate systems under sink and nonsink conditions can be described rigorously according to a generally applicable formula on the basis of the single-particle dissolution model and the initial particle distribution. The kinetic model for log-normal systems dissolving under sink conditions is extended to nonsink conditions as a specific example. The equation presented describes a general class of multiparticulate models for various values of the dispersion parameter and the dissolution capacity coefficient.

Kinetics↗
PubMed1977

Method of obtaining drug-macromolecule binding parameters directly from dynamic dialysis data.

A new method of treating dynamic dialysis data to obtain binding parameters for drug-macromolecule interactions is presented. This method allows the determination of binding parameters directly from dialysis data according to a theoretical model. It is not necessary to determine the dialysis rate constant accurately in a separate experiment, and bias is not introduced due to differentiation. The proposed method should be applicable where the drug is substantially bound to the dialysis membrane.

Albumins↗
PubMed1976

Necrotising enterocolitis of the newborn--is it gas-gangrene of the bowel?

Necrotising enterocolitis (N.E.C.) of the newborn is thought to be caused by ischaemia of the bowel. This would favour the conversion of clostridial spores, which can occur very early in the intestinal tract of newborns, to toxin-producing, invading bacilli. The histology of resected gut specimens from 6 of 7 N.E.C. patients who had undergone operation was similar to that in cases of gas-gangrene of the bowel and that in experimentally provoked pneumatosis cystoides intestinalis. In one case Clostridium perfringens type A was cultured in great number by anaerobic technique. The clostridia in these cases may have played an important role in the development of N.E.C.

Clostridium perfringens↗
PubMed1976

Theoretical isotropic dissolution of nonspherical particles.

Equations are derived for the isotropic dissolution of single particles, considering simple forms of the six crystal systems. These can be summarized by three basic equations which are approximated well, and in some cases exactly, by the dissolution equation for a hypothetical spherical particle of specified diameter. Formulas are given to enable calculation of this diameter and to minimize the weighted errors in the approximations. Spherical approximations provide a simple basis for calculating the dissolution profile of real multiparticulate systems which are difficult to describe otherwise. Spherical approximations based on equal surface area or volume result in large errors.

Crystallization↗
PubMed1976

Experimental evaluation of three single-particle dissolution models.

The dissolution of the 60-85-mesh fraction os recording, flow-through dissolution apparatus equipped with a dissolution cell; it was particularly suitable for kinetic analysis of multiparticulate systems. By using a time-scaling approach, experimental data are compared with theoretical calculations to evaluate, quantitatively, which of three single-particle dissolution models best describes the data and how well the multiparticulate kinetics can be explained mathematically. The nonspherical tolbutamide particles are replaced in the calculations by a hypothetical system of spherical particles that appears to be log-normally distributed. This procedure permits the calculation of the intrinsic dissolution profile, considering both size distribution and particle shape effects.

Kinetics↗
PubMed1975

Dissolution profile in relation to initial particle distribution.

A general equation was derived describing the complete and exact dissolution profile of powders under sink conditions. It is applicable to powders having any initial particle-size distribution, with particles dissolving according to any explicit equation. It was applied to develop an equation for the dissolution of log-normal powders that is more generally applicable than previous approaches. The effect of change in initial particle-size distribution parameters on the dissolution profile is illustrated.

Computers↗
PubMed1975

Size distribution effects in multiparticulate dissolution.

The evaluation of models for single-particle dissolution, based on multiparticulate dissolution data, is complicated by the distribution effect present when the particles are not truly monodispersed. By using simulated data, it is shown that remarkably good linearity can be obtained with log-normal powders using an incorrect model. It is suggested that particle-size analysis is necessary to enable calculation of the distribution effect and to prevent this type of misinterpretation. The change in particle-size distribution during dissolution is calculated and shows potential for distinguishing between two, but not all three, of the models investigated. Four theoretical rules for multiparticulate dissolution are stated and discussed. The concept of "time scaling" is presented. By using this procedure, it should be possible to reduce considerably computational errors arising from nonlinear dissolution data. It is demonstrated that dissolution profiles can be transformed to a standard form, enabling the distribution effect to be evaluated without interference from rate or particle-size parameters.

Kinetics↗