[Characteristics of the set-up of the lymphocyte blast transformation reaction using whole blood].

The authors analyze the specific features of the technique of lymphocyte blastogenesis test (LBGT) with whole blood and of interpreting its results in examinations of healthy donors, patients with hypogammaglobulinemia, chronic bronchitis or pneumonia, and bronchial asthma. The suggested LBGT variant is a sensitive and reproducible technique fit for assessing the immunity status, making use of small volumes (up to 0.1 ml) of the blood; it is recommended for clinical examinations and mass immunologic screenings.

[Effect of human regulatory myelopeptides on the elaboration of a factor inhibiting leukocyte migration].

Some properties of the regulatory peptides from human bone marrow have been investigated. It has been determined that the activity of the regulatory peptides was different in healthy donors and patients with agammaglobulinemia and paraproteinemia.

Early adventures in drug metabolism: 4. Diphenylhydantoin (phenytoin).

This series comes to a close with a discussion of problems related to phenytoin metabolites, their discovery and role in the toxicity of this drug. More particularly, it looks at the influence of the p-hydroxyphenyl metabolite of phenytoin (HPPH) on the metabolic disposition of the parent compound, and the relationship of the dihydrodiol metabolite to the putative presence of arene oxides. The question of pro-drugs is examined, including factors that may influence any decision to market the drug.

Early adventures in drug metabolism. 3. Chloramphenicol.

The saga of our early experiences with drug metabolism studies in the Parke-Davis Research Laboratories continues with a brief resume of the behavior of chloramphenicol under unusual clinical conditions and a consideration of the toxic effects of this drug and its metabolites in laboratory animals and in humans. The dose-related reversible effects of chloramphenicol upon the ferrokinetic pattern and cellular respiration are clearly separated from its nonreversible effects on the bone marrow cells of susceptible individuals. A number of possible research approaches are suggested for the exploration of these problems.

Early adventures in drug metabolism: 2. The absorption of drugs.

This paper deals with our experiences in drug metabolism in the Parke-Davis Research Laboratories at a time when good analytical procedures were just starting to make their appearance and pharmacokinetics was an undiscovered territory. Some of our groping efforts to understand the factors influencing absorption are described. These included formulation differences in generic products and their effect upon absorption.

Early adventures in drug metabolism: 1. Role of the Bratton-Marshall reagent.

The Bratton-Marshall reagent is one of the real land-marks in the development of drug metabolism and pharmacokinetics, coming at a time when highly sensitive and specific analytical procedures were desperately needed for the measurement of drug concentrations in the body. Examples of its applications are taken from early work in the mid-40's and 50's in the Parke-Davis Research Laboratories, extending from primary aromatic amines (e.g.

Discovery of phenytoin.

Numerous letters and reports located in the Parke, Davis and Smithsonian files add to the story of Merritt's and Putnam's discovery of the anticonvulsant (AC) properties of phenytoin. The major events preceding this work were the fortuitous discovery of phenobarbital as an AC agent, structure/hypnotic activity studies with barbiturates and hydantoins in the early 1920s by A. W.

[Effect of levamisole on cellular immunity indices in chronic bronchitis and chronic pneumonia patients].

Based on the study of the immune status in 133 subjects of whom 85 suffered from chronic bronchitis and chronic pneumonia and 50 comprised the group of normal subjects it could be established that patients with chronic bronchitis and chronic pneumonia showed a reduction in the blood of T and B lymphocytes. Administration of levamisole to patients with chronic pulmonary diseases led to an increase of the initially reduced T and B lymphocyte counts. The clinical improvement of patients induced by levamisole correlated with a positive time-course of changes in immunological characteristics.

Bioavailability of calcium valproate in normal men compared with the free acid and sodium salt.

Calcium valproate has been formulated into tablets containing the equivalent of 250 mg valproic acid (VPA). The bioequivalence of this preparation (Valontin, Parke-Davis) has been studied in 12 normal adult males in parallel with other products containing the free acid (Depakene capsules, Abbott) and the sodium salt (Depakene syrup, Abbott). Each subject received a single 500-mg oral dose of each product at 2-week intervals in a randomized three-way crossover study.

Phenytoin metabolism in subjects with long and short plasma half-lives.

Normal adult men with long and short phenytoin plasma half-lives were given 300-mg oral doses of phenytoin once daily for 15 days. Plasma levels of phenytoin (DPH) and its major metabolite (p-HPPH) were measured during the period of drug administration and for 5 days thereafter. Average steady-state plasma levels of DPH rose to 13.

Bioavailability of norethindrone in human subjects.

A competitive protein binding assay for norethindrone was developed to measure plasma levels in human subjects. The plasma levels were considerably higher in women than in men, especially at low dose levels. The plasma levels were directly related to the dose in men; but greater variations in the plasma levels were observed in women.

Simplified fluorometric assay for diphenylhydantoin in plasma.

The fluorometric benzophenone procedure for diphenylhydantoin has been simplified by eliminating the need for preliminary extraction of plasma with an organic solvent. Assays are done directly on 0.2 ml of plasma by treating it with alkaline permanganate to form benzophenone, extracting the benzophenone with heptane, and then shaking the heptane layer with sulfuric acid and measuring the fluorescence of the acid layer.

Effect of an adenosine deaminase inhibitor on the uptake and metabolism of arabinosyl adenine (Vidarabine) by intact human erythrocytes.

Tritium-labeled vidarabine was incubated with fresh citrated human blood in the absence and presence of an adenosine deaminase inhibitor, co-vidarabine was rapidly deaminated to form ara-Hx with minimal incorporation into the erythrocytes. Ara-HxMP was identified as the major component in the erythrocytic nucleotide pool, together with small amounts of IMP, adenosine nucleotides and traces of arabinosyl nucleotides. Addition of the inhibitor completely protected vidarabine from enzymatic deamination and resulted in much greater accumulation of vidarabine 5'-mono-, di-, and triphosphates in the erythrocytes.

The comparative metabolism of zolazepam in rat, dog and monkey.

The metabolic disposition.of zolazepam, a pyrazolodiazepinone, was studied in male and female Spartan rats, Beagle dogs and Rhesus monkeys. Six principal urinary metabolites were characterized by gas chromatography and combined gas chromatography-mass spectrometry.