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Biomedical subjects

B P Spragg

Publications and source records attributed to B P Spragg.

14 recordsLinked to original sources
PubMed1995

Metabolism of beclamide after a single oral dose in man: quantitative studies.

A simple reverse phase HPLC assay is described for the determination of the anticonvulsant compound, beclamide and its 3- and 4-hydroxyphenyl metabolites in urine. Following oral administration of 1 g beclamide to a panel of healthy volunteers, less than 0.4% of the dose was excreted unchanged in the 24-h urine and unconjugated 3- and 4-hydroxyphenyl metabolites were not detected. Based on examination of the urine after incubation with beta-glucuronidase and aryl sulphatase, it was found that these hydroxyl metabolites were excreted as both glucuronide and sulphate conjugates. For each metabolite the glucuronide was the major excretory product (approximately 10:1). The 24-h excretion of the combined conjugated metabolites was 7% (for the 3-hydroxy metabolite) and 24% (for the 4-hydroxy metabolite) of the dose. Approximately 22% of the administered dose of beclamide was excreted as hippuric acid. In view of the simplicity of assay, beclamide may be a useful tool substance with which to examine factors influencing the xenobiotic metabolic pathways of benzene ring hydroxylation and glucuronide and sulphate conjugation in man.

Administration, Oral↗
PubMed1989

Pharmacokinetics of lofepramine and amitriptyline in elderly healthy subjects.

Pharmacokinetics of 3 doses (70 mg, 105 mg and 140 mg) of lofepramine were compared with amitriptyline (50 mg) in 6 healthy drug free elderly subjects aged between 65 and 72 years. Pharmacokinetics of lofepramine in the elderly appear to be similar to young adults as published before. Peak plasma lofepramine and amitriptyline concentrations were achieved at about 1 h and 3 h of dosing respectively. Elimination half-life of lofepramine was 2.5 h and that of amitriptyline was 31 h. A 24-fold inter-individual variation in peak plasma lofepramine concentrations was observed, but amitriptyline levels in plasma showed less variation. Pharmacokinetic parameters of amitriptyline were comparable to other published studies involving elderly people. Compared to placebo and lofepramine, amitriptyline produced drowsiness and dry mouth, reduced salivary volume and increased movement reaction time. These effects correlated with the plasma amitriptyline levels.

Aged↗
PubMed1988

Thiamine status, vitamin supplements and postoperative confusion.

In a prospective, randomized, controlled study an intravenous vitamin B complex and vitamin C preparation was administered pre- and post-operatively to 28 elderly patients with a fractured proximal femur and compared with 32 nonsupplemented postoperative controls. Vitamin supplementation significantly, though only transiently, improved postoperative thiamine status (P less than 0.001), but had no influence on mental state or outcome during the postsurgical period. Therefore, the use of parenteral vitamins for postoperative confusion cannot be justified on a routine basis.

Aged↗
PubMed1988

Stability of isoniazid and acetylisoniazid in saliva.

The stability of isoniazid and acetylisoniazid in saliva was studied under various conditions. Acetylisoniazid was stable at 4 degrees, -20 degrees, and -70 degrees C for up to 5 weeks but isoniazid loss was prevented only by storage at -70 degrees C or by addition of azide and storage at 4 degrees C (but not -20 degrees C) for up to 5 weeks.

Drug Stability↗
PubMed1988

Saliva and plasma concentrations of isoniazid and acetylisoniazid in man.

1. The pharmacokinetics of isoniazid and acetylisoniazid in plasma and saliva were compared following administration of oral and intravenous doses (200 mg) to healthy volunteers and patients. 2. In the 22 subjects studied after oral administration and the six subjects studied after intravenous administration there was complete phenotypic agreement for both slow (t1/2 greater than 130 min) and fast (t1/2 less than 130 min) acetylators using either saliva or plasma. 3. Acetylator phenotyping based on the t1/2 of INH determined using saliva collected at 2, 3, 4, 5 and 6 h after a 200 mg oral dose appears to be as reliable as that based on plasma. 4. Salivary isoniazid concentrations may provide a non-invasive alternative to plasma concentrations.

Administration, Oral↗
PubMed1988

The effect of thyrotoxicosis on isoniazid acetylation.

Isoniazid acetylation was assessed in 10 thyrotoxic patients before and after standard antithyroid therapy. The group contained five fast and five slow acetylators and all remained within the same phenotypic classification when rendered euthyroid. There was no significant change in the elimination half-life of isoniazid between thyrotoxicosis and euthyroidism for the group as a whole or for fast and slow acetylators considered separately. Thyrotoxicosis does not appear to be an important determinant of isoniazid acetylation in man.

Acetylation↗
PubMed1986

The disposition of theophylline in blood in chronic obstructive lung disease.

In 42 subjects with chronic obstructive lung disease receiving chronic oral theophylline therapy, the venous whole blood theophylline concentration was closely related to the total plasma theophylline concentrations (r = 0.976, p less than 0.001). The blood/plasma concentration ratio was 0.85 +/- 0.13 and was not related to the haematocrit or the free fraction of theophylline in plasma. The red blood cell theophylline concentration was closely related and numerically similar to the free plasma concentration. This indicates that the free plasma concentration is the most important determinant of red blood cell concentration, and that binding of drug by red blood cells or active uptake into erythrocytes is unlikely to occur. Whole blood concentration can be used to predict plasma theophylline concentration in subjects with obstructive lung disease in situations where preparation of plasma is inconvenient. The therapeutic range for whole blood concentration is approximately 8.5-17 mg/L.

Adolescent↗
PubMed1985

When is autologous bone marrow transplantation safe after high-dose treatment with etoposide?

Etoposide (VP16-213) is widely used in the treatment of malignant disease and increasingly high doses are now used in conjunction with autologous bone marrow transplantation. After treatment with etoposide, bone marrow should be reinfused as soon as the plasma etoposide concentration has fallen to a level which will not prove toxic to the small number of pluripotential stem cells present in the reinfused marrow, but this level has not been previously defined. Nine patients were studied of whom five received 1400 mg etoposide/m2 and four received 2400 mg etoposide/m2 intravenously over 3 days. Bone marrow was reinfused 64-136 h after finishing chemotherapy. Haemopoietic recovery occurred in all patients within 16 days of autologous bone marrow reinfusion performed at a time when plasma etoposide concentrations ranged from 0-2.42 micrograms/ml. However the clinical and in vitro data presented suggest that bone marrow reinfusion after treatment with high-dose etoposide should be delayed until the plasma etoposide concentrations have fallen to less than 0.4 microgram/ml although haemopoietic recovery may occur after bone marrow reinfusion at higher concentrations.

Adult↗
PubMed1969

A study of the carbohydrate present in three type K macroglobulins.

For a monomeric molecular weight of 180000 three type K macroglobulins (IgM) contained 6-deoxygalactose, mannose, galactose, 2-acetamido-2-deoxyglucose and N-acetylneuraminic acid in the molar proportions 5:38:11:27:7 for Row IgM, 5:31:9:21:7 for Sha IgM, and 5:29:11:26:8 for Tya IgM. The first two proteins were euglobulins whereas Tya IgM was a pseudoglobulin, and therefore the total content of carbohydrate does not appear to be related to the physicochemical properties of the proteins. The three proteins appeared to contain different numbers of oligosaccharide units, Row IgM having about ten units/monomer, and Sha IgM and Tya IgM about eight each. All three proteins had two types of oligosaccharide unit, which by analogy with an immunoglobulin A myeloma globulin were called Type 2 and Type 3 respectively. The Type 2 units had molecular weights equal to or greater than 2000 and contained 1 residue of 6-deoxygalactose, 3-4 of mannose, 1-2 of galactose, 3-4 of 2-acetamido-2-deoxyglucose and 0-2 of N-acetylneuraminic acid. The Type 3 units had molecular weights of less than 2000 and contained 0-1 residue of 6-deoxygalactose, 3-6 of mannose, 0-1 of galactose, 1-3 of 2-acetamido-2-deoxyglucose and no N-acetylneuraminic acid. Glycopeptides corresponding to the two types of unit varied in their aspartic acid content in that most of the Type 3 glycopeptides possessed only 1 residue of aspartic acid whereas most of the Type 2 glycopeptides had an average content greater than 1 residue.

Carbohydrates↗