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Biomedical subjects

V F Smolen

Publications and source records attributed to V F Smolen.

At least 19 recordsLinked to original sources
PubMed1977

Predictive conversion of in vitro drug dissolution data into in vivo drug response versus time profiles exemplified for plasma levels of warfarin.

A mathematical approach to computing the in vivo drug response profiles (such as plasma level, pharmacological response, and urinary recovery versus time curves) corresponding to observed in vitro dissolution of drug dosage form versus time profiles is described. The method is exemplified for warfarin tablets,for which observed in vivo plasma level profiles are compared to corresponding predicted profiles computed from in vitro dissolution data. The potential of the method is demonstrated; approaches to its improvement, as well as its limitations, are discussed.

Computers, Analog↗
PubMed1976

Pharmacokinetics of chlorpromazine-induced miotic response in rabbits.

The time variation of changes in the chlorpromazine-induced pupil diameter decrease was studied following varying bolus and slowly infused intravenous doses administered to rabbits. The observed pharmacological response data were coverted, via, the use of a dose-effect curve, to values theoretically corresponding to relative biophasic drug levels. These values were, in turn, used to construct a linear pharmacokinetic model of the drug bioavailability input equilibrium pharmacological response output dynamics of the system. The use of a time domain, MULTIFIT, computerized method of fitting the data to obtain a pharmacokinetic model was compared to the use of a frequency response, PLTEST, approach. The fidelity of the model in quantitatively relating the time course of systemic drug bioavailability to observed pupil response was verified by the satisfactory agreement obtained by directly comparing experimentally known amounts of drug intravenously infused with corresponding values computed from observed changes in pupil size. The applicability of using pharmacological data for quantitative bioavailability and pharmacokinetic analysis of chlorpromazine is demonstrated. This finding is particularly significant because no suitable chemical or radiological direct assay technique exists for determining levels of chlorpromazine, except for high doses, in body fluids.

Animals↗
PubMed1976

Bioavailability and pharmacokinetic analysis of chlorpromazine-induced rectal temperature depression in rabbits.

Chlorpromazine-induced depression of rectal temperatures in rabbits kept at 20 degrees was used to determine relative biophasic drug levels corresponding to observed hypothermic response intensities, which then served to establish a triexponential linear mathematical model describing drug transference and drug action in this system. Comparisons of various experimentally known, slow intravenous infusion drug inputs of chlorpromazine with drug inputs computed by deconvolution, using the derived model and observed temperature depressions, served to verify the accuracy of the model for the 0.50-4.0 mg/kg dosage range.

Animals↗
PubMed1975

Drug-biomolecule interactions: bioelectrometric study of the mechanism of carbachol interactions with the cornea and its relation to miotic activity.

The augmentation of carbachol miotic activity attributable to enhanced transcorneal absorption, which results from the action of cationic adjuvants included in ophthalmic vehicles, suggested a study of carbachol-corneal tissue interaction as a further step toward understanding the phenomenon. The present study was performed in vivo using an innocuous electrometric technique. A fixed charge density of the corneal epithelial surface versus carbachol concentration profile was obtained from the electrometric results; it revealed three distinct concentration regions defined by precipitous decreases of fixed charge over extremely small concentration ranges. This anomalous behavior is attributed to cooperative alterations in the binding affinities of fixed anionic sites on the tissue surface, which result in an all-or-none release of protons and/or other nicrocations. The unmasked anionic sites become reoccupied with carbachol except in the last region where the reoccupation by carbachol is competitive with other cations in the solution in contact with the surface. This behavior, postulated on the basis of the construction of a carbachol-tissue binding isotherm from which thermodynamic interaction affinities were computed, was corroborated by the observed dependency of the duration of miotic activity on carbachol concentration. Allosteric interactions between anionic binding sites, which are mediated through electron inductive and electrostatic field effects and likely involve a cooperative alteration in tissue water structure, are implicated as underlying the observed phenomena.

Animals↗
PubMed1975

Bioavailability analysis of chlorpromazine in humans from pupilometric data.

Results of studying the time variation of the miotic response intensity for periods of 6 to 8 hours after dosing in up to 16 normal human subjects who received various oral liquid and intravenous doses of chlorpromazine are reported. Relative to oral liquid doses of chlorpromazine syrup, intravenous doses of the drug slowly infused over a consistent time interval of 30 minutes are approximately 11 times as potent in eliciting miotic response activity. Miotic activity was found to be quite dose sensitive as seen from the response vs. time profiles and the dose-effect curves constructed as plots of areas under the response curves and peak response intensities. The dose-effect curves are approximately linear for both intravenous and oral dosing over the majority of the dose ranges studied. Pupilometry is demonstrated as providing a highly sensitive, reliable, rapid and convenient method for detecting differences in both rates and extents of systemic chlorpromazine bioavailability after parenteral or oral dosing with chlorpromazine. Pupilometry allows comparative bioavailability studies to be readily completed for low oral doses, e.g., 10 mg/70 kg, which are not possible to perform even under the most ideal conditions, using the best direct assay techniques presently available. It is precisely at such low oral doses that bioavailability between oral dosage forms are most pronounced and the use of pupilometry has its greatest utility.

Administration, Oral↗