Biomedical subjects

G J Alcorn

Publications and source records attributed to G J Alcorn.

8 recordsLinked to original sources

PubMed1989

Evaluation of a phenytoin dosage regimen design and adjustment computer program.

A computer program for phenytoin (PHT) dosing was developed containing seven different menus: two for drug-naive patients, one using an empirical equation, the other using means for Vmax and Km; two for patients in whom either one or two dose rates and steady-state concentrations are available; two for patients with hypoalbuminemia, and uremia, respectively; and one menu that optimizes Vmax and Km from available steady-state concentrations. The program accepts or converts PHT and sodium PHT, and makes blood level correction for the concomitant administration of 25 different drugs. The evaluation of the program was done by retrospective analysis using data from three study pools: group I involved 47 patients from the University Hospital, group II relied upon 29 patient data supplied from a collaborative Veterans Administration study, and group III involved 26 patients from the Children's Hospital. Predictions were made and compared with found data to be within a range of +/- 15, 20, or 25%. For study group III, many individual blood samples were less than 8 micrograms ml-1; hence, saturation kinetics may not have been involved. It is suspected that saturation kinetics in infants may begin at higher levels. Compliance seems to still be a major problem in PHT monitoring and dosage regimen adjustment. Accepting the data as they are, using one or two dose rates with the corresponding blood concentrations resulted overall in 73-86% achieving blood levels within +/- 25% of the predicted value.

Adolescent↗

PubMed1987

In vivo-in vitro correlations with various aspirin formulations.

In vivo evaluation of gastric irritation as determined by gastric transmural potential difference (GPD) and in vitro characterization of four formulations have been made. The four formulations were: (A) highly buffered, (B) cytoprotective, (C) microencapsulated and (D) a plain tablet. The GPD results showed C to be much less irritating than A or D, and slightly less-irritating than B. The release from all formulations was well represented by dissolution efficiency (DE%) and mean time of dissolution. When correlation coefficients were calculated, significant relationships were found between DE% and the GPD parameters area under the baseline (AUB) and the Reiz Index (RI), and between the mean time of dissolution and the GPD parameters AUB, mean potential drop (MD) and RI.

Adolescent↗

PubMed1985

Triaxial compression of "cappable" formulations.

According to theory, "capping" (visible lamination) occurs at the uniaxial relaxation stage at the point at which the upper punch pressure is released. A method is described whereby the stress in a tablet prone to a "capping" problem can be released in a triaxial manner.

Chemistry, Pharmaceutical↗

PubMed1984

Therapeutic concentration of coumarin as antipyretic.

Using a model previously described the antipyretic effect of coumarin (C) was studied with administration by constant rate infusion. A parallel design was used in the present study with 6 rabbits each in the following groups: (1) control, (2) with C 0.06 mcg/ml as desired steady state concentration for I.V. infusion after a loading dose, (3) endotoxin 0.125 mg/kg I.V. push, and (4) C I.V. Infusion with 0.06 mcg/ml steady state concentration after a loading dose plus endotoxin 0.125 mg/kg I.V. push. C in presence of endotoxin challenge reduces the elevated temperature significantly throughout the entire time of the experiment. Whereas C alone does not cause lowering of normal body temperature, in febrile condition the elevated temperature is reduced to below baseline levels. Based on these and previous findings it is hypothesized that C exhibits an aspirin-like action.

Animals↗

PubMed1984

In vivo-in vitro correlations with sustained-release theophylline preparations.

The in vitro dissolution of four commercially available sustained-release theophylline products was studied. The dissolution of theophylline was evaluated under four conditions: USP-method I or Resotest apparatus, and artificial gastric (pH 3) or artificial intestinal (pH) fluids. The resulting data were evaluated by graphic, first-order transform, dissolution efficiency, non-linear fitting, mean time of dissolution and Weibull analysis methods. The four theophylline preparations and a peroral solution were administered to four male beagle dogs in a cross-over fashion. Parameters were obtained from graphed concentration vs. time data, a one-compartment open model fit, Wagner-Nelson absorption plots, ratios of half values of duration and maximum concentrations, mean times of absorption and analog computer evaluation. Correlations were made between all possible combinations of in vitro and in vivo data by quadrant analysis, Pearson product moment, r, and Spearman rank order correlation methods. A total of 8280 correlation coefficients were calculated. The optimal set of studied conditions for in vivo-in vitro correlations with sustained-release theophylline preparations is the time to reach maximum concentration in the blood (from the fitted data) vs. the time for 15% of the drug to be released into solution from the dosage form (from graphed data) using either the USP I apparatus or the Resotest.

Animals↗

PubMed1983

Cimetidine-theophylline complex formation.

Cimetidine forms a complex with theophylline in vitro in both pH 7.4 buffer and human plasma. The increase in the amount of theophylline in solution is about 20% in the buffer system and about 36% in plasma. It is hypothesized that this complex formation may contribute to and be part of the mechanism of the clinically observed decreased theophylline clearance in man in presence of cimetidine.

Chemical Phenomena↗

PubMedDate not supplied

First-pass elimination of lidocaine in the rabbit after peroral and rectal route of administration.

Lidocaine shows pronounced first-pass metabolism upon peroral administration in man (about 30 per cent peroral bioavailability). Since the rectal bioavailability is about 65 per cent in man it is assumed that some drug is directly absorbed into systemic circulation by-passing the liver. In rats peroral bioavailability is about 8 per cent whereas rectal bioavailability is about 100 per cent. This indicates that the rat is not a suitable model to study rectal lidocaine dosage forms. The purpose of this study was to investigate lidocaine disposition and bioavailability in rabbits after peroral and rectal administration. The peroral bioavailability in rabbits was found to be about 6 per cent and the rectal bioavailability is about 33 per cent. The results indicate that the rabbit is a suitable model for the study of systemic absorption of rectal lidocaine dosage forms.

Administration, Oral↗

PubMedDate not supplied

Antipyretic and pharmacokinetic evaluation of coumarin in the rabbit after endotoxin administration.

The antipyretic effect of coumarin (C) and the drug disposition of C and its metabolites, 7-hydroxycoumarin, 7-HOC, and 7-hydroxycoumarin glucuronide, 7-HOCG, upon endotoxin challenge were studied in an animal model. A parallel design was used with 6 rabbits each in the following groups: control, coumarin 1 mg/kg I.V., endotoxin 0.125 mg/kg I.V., and coumarin 1 mg/kg I.V. plus endotoxin 0.125 mg/kg I.V. C reduces the elevated temperature significantly during the first half hour with the mean temperature difference versus time curve being lower than that for the endotoxin challenged group. Although not significant there is a trend for increased elimination half-life and apparent volume of distribution for C. The apparent volume of distribution for 7-HOC and 7-HOCG increased significantly, and the elimination half-life of 7-HOCG increased significantly.

Animals↗