Search PubMed⌕ Search

Biomedical subjects

M S Roberts

Publications and source records attributed to M S Roberts.

At least 217 records · Page 12Linked to original sources
PubMed1986

The effect of posture on the pharmacokinetics of intravenous benzylpenicillin.

We have studied the pharmacokinetics of intravenously administered benzylpenicillin in normal subjects during bedrest and during ambulation. The values of total body clearance, mean residence time, and renal clearance found during ambulation were 487.4 +/- 100.5 ml/min, 36.23 +/- 13.45 min, and 309.4 +/- 93.4 ml/min (means +/- SD). The corresponding values for bedrest were 543.6 +/- 122.6 ml/min, 35.27 +/- 10.21 min, and 324.1 +/- 145.3 ml/min. There were no significant differences between any of these pharmacokinetic variables with the change in posture. These results differ from previously reported results for the effects of posture on the pharmacokinetics of penicillins administered by extravascular routes, and suggest that the absorption of benzylpenicillin may be dependent on posture.

Adult↗
PubMed1986

The pharmacokinetics of tetrabenazine and its hydroxy metabolite in patients treated for involuntary movement disorders.

The pharmacokinetics of tetrabenazine and a metabolite, hydroxytetrabenazine, have been investigated in seven patients being treated for involuntary movement disorders. Tetrabenazine had a very low oral systemic availability (mean 0.049 +/- 0.032 SD). First-pass metabolism to hydroxytetrabenazine was extensive, and the systemic availability for this metabolite was high (mean 0.81 +/- 0.30 SD). Since hydroxytetrabenazine has been reported to be as active as tetrabenazine in depleting brain amines, and is present at much higher plasma concentrations than the parent drug, it is likely that this metabolite is the more important therapeutic moiety.

Blood Proteins↗
PubMed1986

A dispersion model of hepatic elimination: 1. Formulation of the model and bolus considerations.

A dispersion model of hepatic elimination, based on the residence time distribution of blood elements within the liver, is presented. The general rate equations appropriate for describing the hepatic output concentration of a tracer solute are derived. Particular consideration is given to events following a bolus input dose of a tracer. The model is shown to be compatible with the known hepatic architecture and hepatic physiology. The model has been fitted to hepatic outflow data for red blood cells, albumin, and other noneliminated solutes. The experimental data suggest a high degree of dispersion of blood elements within the liver. The model has also been used to evaluate the effects of changes in enzyme activity, hepatic cell permeability, blood flow, and protein binding on the outflow concentration vs. time profiles of solutes.

Animals↗
PubMed1986

A dispersion model of hepatic elimination: 2. Steady-state considerations--influence of hepatic blood flow, binding within blood, and hepatocellular enzyme activity.

The dispersion model of hepatic elimination is based on the distribution of residence times of blood elements within the liver. The model has two asymptotic solutions corresponding to the "well-stirred" model (complete mixing of blood elements) and the "parallel-tube" model (no variation in residence times of blood elements). The steady-state form of the dispersion model relevant to pharmacokinetic analysis is developed and explored with respect to changes in blood flow, in binding within blood, and in hepatocellular enzyme activity. Literature data are used to evaluate discrepancies among the predictions of the dispersion, well-stirred, and tube models. It is concluded that the dispersion model is consistent with the data. The limitations of steady-state perfusion experiments to estimate the residence time distribution of blood elements within the liver are considered.

Administration, Oral↗
PubMed1986

A dispersion model of hepatic elimination: 3. Application to metabolite formation and elimination kinetics.

A dispersion model of hepatic elimination is presented to describe metabolite formation and elimination kinetics within the liver, consistent with the known physiology and biochemistry of this organ. The model is based on the spread in residence times of blood flowing through the liver. This dispersion model is shown to be more consistent with transient and steady-state data obtained after the single passage of phenacetin and acetaminophen through the liver (both normal and retrograde perfusions) than other models of hepatic elimination. The dispersion model is suitable for the evaluation of enzyme heterogeneity using experimentally obtained metabolite data.

Acetaminophen↗
PubMed1986

The effects of different doses of some acetylsalicylic acid formulations on platelet function and bleeding times in healthy subjects.

In an attempt to find the most appropriate dose and formulation(s) of acetylsalicylic acid (ASA) for thrombosis prophylaxis, healthy volunteers were given doses of ASA for 1 wk daily ranging from 50 to 3900 mg as either Aspro-Clear (soluble), Astrix (enteric coated pellets) or Ecotrin (enteric coated tablets). Platelet function and bleeding times were monitored. All doses of ASA significantly inhibited platelet function (p less than 0.05) and increased bleeding times (p less than 0.05) relative to control values. Irrespective of the formulation, maximum increases in bleeding time and platelet dysfunction were obtained with daily doses of about 100 mg, and no further changes were observed with higher doses.

Adult↗
PubMed1986

Correlation between in-vitro microsomal enzyme activity and whole organ hepatic elimination kinetics: analysis with a dispersion model.

A new model, the dispersion model of hepatic elimination, is applied to the correlation between in-vitro microsomal data and corresponding rat isolated perfused liver data for a number of drugs reported in the literature, whose extraction ratio varies over the range of 0.01 to 0.995. The dispersion model described the data better than either the 'well-stirred' model or the 'parallel-tube' model, two other widely used models of hepatic elimination. The experimental data support the concept that elimination of solutes is affected by is a considerable dispersion on passage through the liver.

Animals↗
PubMed1986

Functional capacity and treatment data from a community based study of patients with rheumatoid arthritis.

A community based study of rheumatoid arthritis was undertaken to determine patient characteristics and the patterns of treatment. Three hundred and eighty subjects were visited in their homes throughout Tasmania (pop. 430 000) by a research team. The median age of the sample was 60 years (interquartile range (IR) 49-69), with a female predominance of 2.65 to 1. The average onset age was 41 years (IR 30-53). Prescribing data indicated that polypharmacy was not common in the community, and that the use of slow acting antirheumatic drugs (SAARDs) and oral corticosteroids was not widespread. At the time of the study 26% of subjects were assayed fully functional--class I of the American Rheumatism Association's (ARA) functional classifications. The functional capacity data provided evidence that the spectrum of rheumatoid arthritis found in the community differed from that found in specialist rheumatology clinics.

Aged↗
PubMed1986

Relationship between methaemoglobin production and methylene blue plasma concentrations under general anaesthesia.

Recently, a family tree with a predisposition for the gene of multiple endocrine neoplasia Type 1 has been identified in Tasmania. As the surgical identification and localisation of parathyroid adenomas is facilitated by the administration of methylene blue, an opportunity has presented to measure the plasma concentration of methylene blue and methaemoglobin production. The study was undertaken to establish whether significant methaemoglobin concentrations were generated during the infusion and whether these concentrations could be related to the corresponding methylene blue concentrations. Mean peak methylene blue concentrations of 3.72 micrograms l-1, mean percentage methaemoglobin of 10.0 and a PaO2 within acceptable clinical ranges were found. No apparent relationship between methylene blue concentration and methaemoglobin production was found.

Adenoma↗
PubMed1986

Distribution and metabolism of nitroglycerin and its metabolites in vascular beds of sheep.

The disposition of nitroglycerin (NTG) and its metabolites has been examined in anesthetised sheep after infusion of 0.4, 5.7 and 22.1 micrograms of NTG/min/kg through the right femoral vein. Several blood samples were collected from the left ventricle, pulmonary artery, left femoral artery, left femoral vein, portal vein and hepatic vein. Significant extraction of NTG across all vascular beds was demonstrated. The extraction was shown to be dose-dependent reflecting hemodynamic and metabolic events. Evidence for metabolism of NTG was provided by the formation of the dinitro and mononitrate metabolites. A preliminary study also showed that administration of the dinitroglycerin significantly impaired NTG metabolism across the hind leg without affecting markedly the hemodynamic response associated with the infusion of NTG.

Animals↗
PubMed1985

The effect of aging on the structure and function of liver messenger RNA.

The size of the poly(A) segment of poly(A)+RNA extracted from hepatocytes isolated from 4- to 30-month-old rats was determined using polyacrylamide-agarose gel electrophoresis. The average size of the poly(A) segment isolated from newly synthesized poly(A)+RNA was 150 nucleotides, and the average size of the poly(A) segment isolated from the steady state pool of cytoplasmic poly(A)+RNA was 70 nucleotides. No significant age related change in either the size or the heterogeneity of the newly synthesized poly(A) segment was found. The translational activity of poly(A)+RNA isolated from livers of 4- to 30-month-old rats was determined using wheat germ extract and rabbit reticulocyte lysate cell-free systems. No age-related change in the translational activity of the poly(A)+RNA was observed. The effect of aging on the cap structure was also studied by measuring the inhibition of cell-free translation by 7-methyl guanosine-5'-monophosphate. No age-related change in the sensitivity of the poly(A)+RNA preparations to inhibition of translation by 7-methyl guanosine-5'-monophosphate was observed. Therefore, the results of this study demonstrate that no major age-related change occurs in the structure of the poly(A) segment, the translational activity, or the cap structure of poly(A)+RNA from rat liver.

Aging↗
PubMed1985

Comparison of models describing the sorption of nitroglycerin and diazepam by plastic infusion systems: diffusion and compartment models.

The time course of sorption of diazepam and nitroglycerin from aqueous solutions into plastic materials has been represented by the diffusion and compartmental models for a variety of storage conditions. The diffusion model seemed to be the more satisfactory model in respect to both description and prediction of the drug uptake for all conditions. The compartment model appeared to be useful for describing the drug uptake at earlier times, giving a satisfactory fit to the data and reliable final parameter estimates. However, that model was not able to describe the loss as equilibrium was approached or accurately predict the disappearance profiles for these solutes with alterations in solution volume or infusion bag size. Approximations of the diffusion model gave parameter estimates consistent with those obtained by nonlinear regression using the full equations.

Adsorption↗
PubMed1985

Community Surveillance Study--perceived response of rheumatoid arthritis patients to NSAIDs.

The perceived effectiveness of nonsteroidal anti-inflammatory drugs was studied in a community population (n=380). The population characteristics of a sample were similar to previous studies. Most patients were on a single NSAID. Rheumatoid arthritis (RA) was found to have a significant impact in terms of disability and lifestyle. Active inflammation was the main incentive to comply with therapy. However, the patients perceptions about the efficacy of the medication, their attitude towards the medication and their motivations for taking it, also affected compliance. A decreased effectiveness of therapy may also be due in part to tolerance to some medications and some evidence of the induction of salicylate metabolism has been reported. Considerable variation in the patients' perception of other forms of therapy for RA were also observed.

Aged↗
PubMed1985

Nitroglycerin disposition in human blood.

The disposition in vitro of nitroglycerin (GTN) and its metabolites in erythrocyte suspensions, plasma and blood has been studied using labelled (3H) and unlabelled GTN and GTN metabolites separated by HPLC. GTN was rapidly metabolised (t1/2 3 min) to dinitro-metabolites and subsequently to the mononitronitrates in erythrocyte suspensions containing a therapeutic concentration of GTN (0.8-10 ng/ml). The metabolism of GTN and its dinitro-metabolites was concentration dependent. GTN and its dinitro-metabolites were plasma protein bound (11-60%). They had an apparent erythrocyte-plasma partition coefficient in the range 0.6 to 0.9. The metabolism of GTN by erythrocytes was partially inhibited by the presence of the dinitro-metabolites of GTN. The metabolism of GTN in blood samples collected from patients could be stopped by adding the collected blood to chilled tubes containing the enzyme inhibitor iodoacetamide.

Biotransformation↗
PubMed1985

Effect of dietary restriction on liver protein synthesis in rats.

At 6 wk of age, male Fischer F344 rats were fed a purified, casein-based diet either ad libitum or in the amount of 60% of the diet consumed by the rats fed ad libitum (restricted diet). Hepatocytes were isolated from the rats between 2.5 and 19 mo of age. The protein content of the hepatocytes isolated from the rats fed the restricted amount of diet was significantly lower than that of hepatocytes isolated from rats fed ad libitum. The DNA and RNA content of the hepatocytes were similar for the rats fed the two dietary regimens. The absolute rate of protein synthesis for hepatocytes isolated from rats fed ad libitum decreased 55% between 2.5 and 19 mo of age. However, the rate of protein synthesis by hepatocytes from rats fed the restricted amount of diet decreased only slightly with increasing age. At 19 mo of age, the rate of protein synthesis by hepatocytes from the rats fed the restricted amount of diet was significantly higher than the rate of protein synthesis for hepatocytes from rats fed ad libitum. Therefore, dietary restriction retards the age-related decline in liver protein synthesis.

Aging↗