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Biomedical subjects

D J Cutler

Publications and source records attributed to D J Cutler.

At least 73 records · Page 4Linked to original sources
PubMed1987

On the mechanism of transport of salicylate and p-hydroxybenzoic acid across human red cell membranes.

The pH-dependence of efflux of salicylate and p-hydroxybenzoic acid (PHB) from human red cells indicates that the un-ionized species penetrates the membrane. No effect of the anion channel blocker 4,4'-diisothiocyano-2,2'-disulphonic stilbene was observed. The temperature-dependence of efflux suggests that the energy barrier to transport of salicylate and PHB is the transfer of the acids from water into the membrane, rather than transport through the membrane interior. Intracellular binding of both acids was found to be pH-dependent.

Biological Transport↗
PubMed1986

In vitro binding of chloroquine to rat muscle preparations.

Chloroquine (7-chloro-4-[[4-(diethylamino)-1-methylbutyl]amino]quinoline; CQ) accumulates in the insoluble fraction of rat muscle homogenates with an equilibrium distribution ratio of 7.8 L/kg. This is of a similar magnitude to muscle:plasma ratios observed in vivo. Uptake is approximately linear, even up to concentrations of free CQ greatly exceeding toxic plasma levels. Cell structural integrity is not essential for uptake, indicating that CQ is bound to tissue constituents and not trapped inside cells by an active process. At pH 7.4, binding of ionized CQ at anionic sites on tissue predominates over lipid partitioning of the un-ionized species. Binding to phospholipids is a major component of total muscle binding.

Animals↗
PubMed1986

Drug availability to noneliminating tissues and sites of action following an intravenous dose.

It is shown that for drugs with high clearance, administered as an intravenous (iv) bolus, the amount of drug available to noneliminating tissues may be significantly less than the administered dose. This arises as a result of recirculation and elimination of some drug within an eliminating circuit, without contact of the drug with tissues outside the eliminating circuit. The same effect also influences drug availability to noneliminating tissues following an oral dose. The relative availability of a drug to sites of action and drug toxicity are also discussed and shown to depend on clearance and blood flow to these sites.

Administration, Oral↗
PubMed1986

The pH-dependence of chloroquine uptake by phosphatidylcholine vesicles.

The pH-dependence of chloroquine uptake by phosphatidylcholine bilayered vesicles was investigated to examine the relative affinity of ionized and un-ionized chloroquine species to membrane bilayers. The results suggest that the neutral species and monocation are taken up by the bilayers but only the un-ionized species interacts significantly with the hydrocarbon interior.

Chloroquine↗
PubMed1985

High-performance liquid chromatographic assay for hydroxychloroquine and metabolites in blood and plasma, using a stationary phase of poly(styrene divinylbenzene) and a mobile phase at pH 11, with fluorimetric detection.

A sensitive rapid high-performance liquid chromatographic assay for hydroxychloroquine and three major metabolites, desethylhydroxychloroquine, desethylchloroquine and bisdesethylchloroquine, has been developed. An ion-suppression separation technique is used with a macroporous polymer, poly(styrene divinylbenzene), stationary phase and a mobile phase of methanol--water with triethylamine, pH 11. A single ether extraction from alkalinized plasma or whole blood, with chloroquine added as an internal standard, is used. Using fluorescence detection, with excitation at 337 nm, the limit of sensitivity is 1 ng/ml. Some anti-inflammatory drugs which may be used concurrently for rheumatoid disorders are shown not to interfere with the assay. Samples of whole blood and plasma obtained from rheumatoid patients contained hydroxychloroquine and all three metabolites.

Anti-Inflammatory Agents↗
PubMed1981

Properties of the recirculation model: matrix description and conditions for a monotonic decreasing single pass response.

The recirculation equation is examined for the case in which the blood concentration is given by a polyexponential expression sigma Ai exp (-ait). A matrix is developed whose eigenvalues are the exponential coefficients of the single pass response. These eigenvalues are real and distinct, and the single pass response is monotonic decreasing, when the Ai are all positive. An ordering relatión for the eigenvalues is given.

Blood Circulation↗
PubMed1981

Properties of the recirculation model: calculation of the amount of drug in the body from blood concentration data, with application to absorption rate calculations.

Compartment models express the relationship between amounts and concentrations by volumes of distribution, which are fundamental parameters of the models. For a recirculation model, the amount of drug in the body is given by the convolution of the measured blood concentration with a function, termed the retention function, which is a characteristic of the system. The amount of drug in the body can be partitioned into rapidly recirculating and slowly recirculating portions, which are analogous to the amounts of drug in the central and peripheral compartments of a compartment model. A method of calculating absorption rates is presented that is comparable with the Wagner-Nelson and Loo-Riegelman methods, but makes fewer assumptions.

Blood Circulation↗
PubMed1980

Hemochromatosis heart disease: an unemphasized cause of potentially reversible restrictive cardiomyopathy.

Cardiac involvement in hemochromatosis typically results in congestive cardiomyopathy; a restrictive cardiomyopathy due to hemochromatosis is distinctly rare. A restrictive cardiomyopathy, which developed in the patient described in this report, was due to hemochromatosis which mimicked constrictive pericarditis clinically, echocardiographically and hemodynamically, and resulted in a thoracotomy for attempted surgical therapy. The fact that hemochromatosis represents the only cause of a restrictive cardiomyopathy that is potentially reversible by medical therapy makes early recognition of hemochromatosis heart disease important.

Cardiomyopathies↗
PubMed1979

A linear recirculation model for drug disposition.

A new approach to the modeling of drug disposition is described. Disposition is regarded as the result of repetitive passes of the drug around the circulation. Mathematical analysis of experimental blood concentration data yields an expression describing the kinetics of a single pass through the tissues. In physicochemical terms the single-pass behavior depends to a large extent on the interaction of the drug with individual tissues, which greatly simplifies interpretation. The method may reveal features of disposition not apparent from experimental blood concentration data.

Kinetics↗
PubMedDate not supplied

Definition of mean residence times in pharmacokinetics.

A new definition of the mean residence time is proposed which includes the commonly used definition as a special case. The advantage of the new definition is that it applies for both linear and non-linear systems. Some practical advantages which follow from the new definition are discussed. Procedures for using urinary excretion data in mean residence time estimation are discussed.

Humans↗