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Biomedical subjects

M S Roberts

Publications and source records attributed to M S Roberts.

At least 235 records · Page 13Linked to original sources
PubMed1985

Determinants of compliance in rheumatoid arthritic patients assessed in their home environment.

Patient compliance with prescriber's medication instructions was investigated in 178 rheumatoid arthritis patients treated in community practice. The compliance rate in the sample subjects was estimated to be 63.5%. Disease activity, measured objectively with erythrocyte sedimentation rate (ESR) and subjectively by duration of morning stiffness, was a major incentive for adherence to the treatment regimen. Among subjects with active disease (ESR greater than 20 mm in 1 h), the rate of compliance was 73.8%, but this fell to 52.7% among those with a normal ESR (i.e. ESR less than or equal to 20 mm in 1 h). The motivations and perceptions of the subjects concerning their drug therapy also affected compliance. Compliance was however less dependent on perceptions when active inflammation was present.

Administration, Oral↗
PubMed1985

The pharmacokinetics and bioavailability of a tracer dose of [3H]-mebendazole in man.

Five volunteers, whose ages ranged between 37 and 64 years, took part in a crossover study to determine the pharmacokinetics and bioavailability of mebendazole in man following intravenous and oral administration of a tracer dose of [3H]-mebendazole. Following intravenous administration, the average distribution half-life, elimination half-life and rate of clearance were 0.20 h, 1.12 h, and 1.063 min respectively. After oral administration of the solution, the average elimination half-life was 0.93 h, the apparent rate of clearance was 0.846 l/min, the average time to peak plasma concentration was 0.42 h, and the bioavailability of mebendazole was 22%. Comparison of metabolite area under the plasma concentration vs time data from each route of administration indicates that absorption of mebendazole from the gastrointestinal tract at this dose level is almost complete. The low bioavailability observed following oral administration at this dose level is postulated to be due to high first pass elimination. Approximately half of the administered dose of radioactivity following intravenous and oral administration was detected in the urine, and the major unconjugated metabolite of mebendazole was found to be 2-amino-5(6) [alpha-hydroxybenzyl]benzimidazole (IV), not 2-amino-5(6)benzoylbenzimidazole (II), as previously reported.

Absorption↗
PubMed1985

The effect of iontophoresis and vehicle pH on the in-vitro permeation of lignocaine through human stratum corneum.

The effect of iontophoresis and the pH of aqueous vehicles on the rate and extent of permeation of lignocaine through excised human stratum corneum was investigated. In the absence of iontophoresis, the rate of penetration was greatest at the higher pH values where lignocaine exists mainly in the unionized form; iontophoresis was most effective at the lower pH values where lignocaine is mainly ionized. At pH 3.4, and 5.2, the flux increased during iontophoresis, by approximately 8.5 and 4 times, respectively, relative to that occurring without iontophoresis. The present results suggest that some weak electrolytes which show poor percutaneous penetration may be administered topically using iontophoresis provided the drug is kept in a highly ionized form.

Humans↗
PubMed1985

Metabolite inhibition of nitroglycerin metabolism in sheep tissue homogenates.

The metabolism of nitroglycerin in sheep tissue homogenates has been examined using tritiated nitroglycerin and a HPLC separation procedure. Nitroglycerin was metabolized by liver, lung, muscle, arterial and venous tissue to its dinitrometabolites and subsequently to mononitroglycerin. Addition of the dinitrometabolites substantially inhibited the degradation of nitroglycerin in all tissue homogenates.

Animals↗
PubMed1984

Dynamics of clomethiazole edisylate interaction with plastic infusion systems.

The dynamics of the interaction of clomethiazole edisylate (1) with polyvinyl chloride and cellulose propionate, the main plastics used in the manufacture of infusion bags and sets, was examined. An experimental system in which the plastic was either open or closed to the environment was used to determine the relative contribution of the sorption and permeation processes to loss from solutions of clomethiazole edisylate (I) in contact with the plastic infusion systems. Sorption by the plastic infusion materials accounted for most of the drug loss, while permeation into the external environment accounted for the remainder. The sorption and permeation into and through polyvinyl chloride was temperature dependent. The diffusion coefficient and permeation rate constant both increased with temperature, while the polyvinyl chloride-water partition coefficients were independent of temperature. The activation energy for the diffusion in polyvinyl chloride was 13.5 kcal/mol. The permeability of the infusion bag plastic and the evaporation across an unstirred air boundary layer adjacent to the external surface of the plastic both appeared to contribute to the overall diffusional resistance encountered in the permeation process. The plastic-water partition coefficients are independent of initial concentration, suggesting that the concentration-dependent loss of the drug from solutions stored in plastic infusion bags and burets is a result of the greater diffusivity of the drug in the plastic at the higher initial concentrations. Plasticization of the polymers by the drug is indicated by the increase in the diffusivity of the drug in polyvinyl chloride and cellulose propionate, the increase in the rate and extent of sorption of a radiolabeled marker (diazepam) by the plastic, and the decreased stiffness of polyvinyl chloride exposed to higher concentrations of the drug.

Chlormethiazole↗
PubMed1984

A rapid method for determination of acetylation phenotype using dapsone.

A rapid, simple one-stage protein precipitation method for the estimation of plasma dapsone (DDS) and monoacetyldapsone (MADDS) concentration by high-pressure liquid chromatography (h.p.l.c.) is described. Its performance in the assignment of acetylator phenotype was compared with a reference h.p.l.c. method utilising an extraction procedure and internal standard. The rapid h.p.l.c. technique combined with measurement of the plasma MADDS/DDS ratio is, in our opinion, the method of choice for the determination of the acetylator phenotype in population studies.

Acetylation↗
PubMed1984

Fate of chlorbutol during storage in polyethylene dropper containers and simulated patient use.

The disappearance of chlorbutol from aqueous solutions stored in polyethylene containers under various experimental and simulated patient use conditions is described. Chlorbutol is lost by sorption into the container wall, container insert and by permeation into the external environment. The extent of chlorbutol loss from solution and uptake by the container components is dependent on temperature, chlorbutol concentration and the closure used. Aqueous chlorbutol solutions stored in the polyethylene container evaluated have a predicted shelf-life (time for 10% loss) of about 4 months at 25 degrees C and 8 months at 20 degrees C. Negligible loss is found during simulated patient use over 1 month.

Chlorobutanol↗
PubMed1984

An audit of therapeutic drug monitoring procedures--use of theophylline assay services.

Monitoring therapy involving drugs exhibiting high intersubject variation and/or narrow therapeutic index has become more generally accepted in hospitals. This paper describes an audit conducted jointly by clinical pharmacists and clinical biochemists into the use and therapeutic value of a drug monitoring service in a general hospital using theophylline as a model. Assay values were categorized as 'subtherapeutic', 'therapeutic' or 'potentially toxic'. The reporting procedures involving the two departments were evaluated along with action taken by the requesting clinicians. The study showed that 60% of the theophylline assay results fell within the therapeutic range at the time of sampling. However only 38% of samples were considered to have been taken under steady state conditions. There was a significant delay in relaying the results to the clinicians. Procedural changes involving sampling times, analytical techniques, recording and conveying results to clinicians and co-operative policies between the departments of pharmacy and clinical chemistry have been implemented as a result of this study.

Adult↗
PubMed1984

Inhibition of platelet function by a controlled release acetylsalicylic acid formulation--single and chronic dosing studies.

The extent to which a controlled release acetylsalicylic acid (ASA) formulation inhibited platelet function has been evaluated in single and chronic dosing studies. In the single dose study, the platelet inhibitory effect of the controlled release formulation was compared with that of an equivalent dose of soluble ASA and an equimolar dose of sodium salicylate (SA). In the chronic dosing study, ASA dose-response curves for platelet function, including cyclooxygenase activity, were determined for various doses (20-1300 mg) of the controlled release (enteric coated pellets) ASA formulation taken by volunteers daily for one week. Platelet function was assessed by the degree of inhibition of aggregation for several aggregating agents, and the degree of inhibition of activity of platelet cyclooxygenase quantified by the estimation of malondialdehyde (MDA) production. Plasma ASA and SA concentrations were also determined in each study. The controlled release product inhibited platelet function to the same extent as an equimolar dose of soluble ASA, but did so with much lower and sometimes undetectable peak systemic plasma ASA concentrations. SA, the direct metabolite of aspirin, did not have any effect on platelet function. The ASA dose-platelet function response curves obtained from chronic dosing with the controlled release formulation appeared to be similar to those reported previously for the soluble product. The inhibition of platelet function appeared to be unrelated to plasma ASA concentrations.

Adult↗
PubMed1983

Cyst and host tissue concentrations of mebendazole in patients undergoing surgery for hydatid disease.

Mebendazole levels were assayed by high performance liquid chromatographic assay in plasma, host tissues, and hydatid material taken from four patients who underwent surgery for hydatid disease. The drug was absorbed and had penetrated both into the host and into the parasite material. The levels of the drug in viable hydatid cysts were much lower than those in dead cysts. The possibility of exclusion or detoxification of the drug by viable hydatid cysts is raised.

Benzimidazoles↗
PubMed1983

Direct quantitative determinations by multiple metastable peak monitoring. 1--Warfarin in plasma.

A technique for the direct quantitative determination of plasma warfarin concentrations has been developed using multiple metastable peak monitoring on a double focusing mass spectrometer of normal geometry. The method uses a direct insertion probe and requires no sample purification or derivatization. Deuterated warfarin was added as an internal standard, and the first field free region metastable fragmentations for the loss of an acetyl radical from the molecular ion of both warfarin and internal standard were monitored. These independent daughter ions were focused by a simple combination of linking the magnetic and electric sectors, accelerating voltage switching and selected ion monitoring using standard instrumentation. Results were acquired and processed by normal selected ion monitoring software. Repeated determinations of plasma warfarin concentrations were made with plasma extracts representing approximately 4 microliter of plasma, each sample taking two minutes to process by this technique.

Humans↗
PubMed1983

Pharmacokinetics of aspirin and salicylate in elderly subjects and in patients with alcoholic liver disease.

Plasma aspirin, salicylate and salicyluric acid concentrations were monitored in young, elderly and alcoholic subjects after ingestion of a single 1.2 g dose of soluble aspirin. The plasma aspirin, salicylate and unbound salicylate concentration-time profiles varied considerably between individual subjects. Most of the pharmacokinetic parameters derived from these profiles were not significantly different between young subjects, elderly subjects and subjects with alcoholic liver disease. Individual plasma albumin concentrations provided a better index of the unbound plasma salicylate clearances and salicylate plasma protein binding than the age of the subject or the presence of alcoholic liver disease. Highest unbound plasma salicylate concentrations were found in subjects with the lowest plasma albumin concentrations.

Adult↗
PubMed1983

Factors affecting the availability of diazepam stored in plastic bags and administered through intravenous sets.

Factors affecting the loss of diazepam from i.v. admixtures to flexible polyvinyl chloride (PVC) bags and to various administration sets were studied. Admixtures containing diazepam and 0.9% sodium chloride injection were stored for up to 550 hours in flexible PVC bags and in glass vials at various temperatures. Diazepam injection containing two different solvents was used. Initial diazepam concentrations in storage studies ranged from 25 to 100 micrograms/ml and pH ranged from 4.2 to 7.5. To determine availability of diazepam after infusion through administration sets, solutions (50 micrograms/ml) from glass containers were run through six different sets at 1 ml/min for seven hours. In storage studies, the difference in composition of the solvent was found to have only a slight effect on the rate and extent of diazepam loss. Diazepam loss was unaffected by pH. For admixtures stored in 1000-ml flexible PVC bags, the fractional loss of diazepam was greater at small volumes. The diazepam concentration of solutions in flexible PVC bags decreased more rapidly during infusion than during storage of the total original volume. The fraction of diazepam remaining in stored solutions was independent of the initial concentration, but the rate and extent of diazepam loss was greater at higher temperatures. Diazepam loss was dependent on length of flexible PVC tubing, and diazepam availability was greater with faster flow rates. In solutions infused through the polyolefin Tridilset, 100% of the diazepam remained. When storage of diazepam admixtures in PVC bags or administration through PVC tubing cannot be avoided, measures to minimize the rate and extent of diazepam loss include decreasing the temperature and the storage time and increasing the surface-area-to-volume ratio and the flow rate. Equations are presented for calculating the amount of diazepam delivered.

Adsorption↗
PubMed1982

Clinical pharmacokinetics of high dose mebendazole in patients treated for cystic hydatid disease.

The plasma concentrations of mebendazole and its metabolites have been monitored in twelve patients after receiving a 10 mg/kg dose for cystic hydatid disease. The mebendazole plasma concentration-time profiles differed considerably between patients; elimination half-lives ranged from 2.8-9.0 h, time to peak plasma concentration after dosing ranged from 1.5-7.25 h and peak plasma concentrations ranged from 17.5 to 500 ng/ml. The mean peak plasma concentration of mebendazole after an initial dose (69.5 ng/ml) was lower than found in patients during chronic therapy (137.4 ng/ml). The plasma AUCTS for the major metabolites of mebendazole (methyl 5-(alpha-hydroxybenzyl)-2-benzimidazole carbamate and 2-amino-5 benzoylbenzimidazole) were about five times the plasma AUCT found for mebendazole in patients on chronic therapy. It is suggested that the slower clearance of these polar metabolites relative to mebendazole results from enterohepatic recycling. Since mebendazole is also highly plasma protein bound, caution should be observed in administering mebendazole to patients with liver disease. Concentrations of mebendazole found in the tissue and cyst material collected from two patients during surgery ranged from 59.5 to 206.6 ng/g wet weight.

Adult↗
PubMed1982

Interactions between drugs and intravenous delivery systems.

The loss of 45 drugs from intravenous solutions during simulated infusions through plastic infusion sets; factors affecting such losses; and ways to minimize these losses are investigated. A total of 43 drugs was studied in 0.9% sodium chloride solution; one drug was in 5% dextrose solution and one in a solvent supplied by the manufacturer. Drug loss was studied in plastic infusion sets, with and without burette chambers, and glass infusion bottles; polyethylene and silastic tubing with glass syringes on an infusion pump; and single-use all-plastic syringes. Variables studied were flow rates, infusion times, drug concentrations, pH, and tubing lengths and radii. Clomethiazole edisylate, chlorpromazine hydrochloride, diazepam, promazine hydrochloride, promethazine hydrochloride, thiopental sodium, thioridazine hydrochloride, and trifluoperazine dihydrochloride were lost from solution during infusions through at least one system. The loss of most drugs during infusion was slow, time-dependent, and concentration-independent, indicating a diffusion-controlled sorption process rather than a binding, adsorptive process. Drug loss was lowest in short lengths small-diameter tubing with low permeability constants. None of the drugs was lost stored in all-plastic single-use syringes. It is concluded that loss of drugs through sorption processes can be minimized by administering infusions through short lengths of small-diameter tubing made of inert plastics.

Adsorption↗