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Biomedical subjects

I J Smith

Publications and source records attributed to I J Smith.

At least 37 records · Page 2Linked to original sources
PubMed1995

The influence of regional deposition on the pharmacokinetics of pulmonary-delivered human growth hormone in rabbits.

The pulmonary deposition and pharmacokinetics of human growth hormone (hGH), administered by aerosol and instillate, in formulations containing 99mTc-DTPA (for gamma scintigraphic imaging) have been studied in five male New Zealand White rabbits. Gamma scintigraphy indicated that the peripheral:central deposition tended to be greater for aerosol (1.54) than for instillate (0.8). Two gamma scintigraphic methods were used to quantify dose deposited by aerosol, which permitted bioavailabilities to be determined. The bioavailable fraction for aerosolized hGH (45%) was greater than for instilled hGH (16%). This was attributed to the differential effects of mucociliary clearance. Absorption rate limited pharmacokinetics prevailed for both hGH formulations with post-peak half-lives approximately 10-fold greater than the intravenous elimination half-life of 40 min. Apparent absorption rate constants resulting from instillation and aerosolization were equivalent (0.0012 min-1 and 0.0020 min-1 respectively), however lung-to-blood transfer rate constants for aerosol delivery (0.00071 min-1) were greater than for instillation (0.00018 min-1).

Administration, Inhalation↗
PubMed1995

The challenge of reformulation.

All current metered dose inhalers (MDIs) contain chlorofluorocarbons (CFCs) as the propellant. Two alternative hydrofluoroalkane propellants, HFA134a (tetrafluoroethane) and HFA227 (heptafluoropropane), are being investigated. The replacement of CFCs by HFAs has a major impact on all aspects of the MDI from the basic formulation to the tests required to assess performance. All commonly used surfactants are essentially insoluble in the HFA propellants. The performance of the metering valve is critical to reproducible delivery of drug from an MDI. However, the properties of the two HFA propellants are so different from CFCs that new elastomeric seals have had to be developed. The current CFC11 propellant, which is a liquid at low room temperatures, allows the drug to be introduced into the MDI as a liquid suspension before the metering valve is sealed to the canister. Both HFAs are gases at normal temperature and atmospheric pressure, therefore all handling as a liquefied propellant must be performed under high pressure in totally sealed systems. To ensure adequate performance of non-CFC MDIs new tests and standards have been developed and introduced. The development of non-CFC MDIs represents a challenging task to provide new, safe and efficacious MDI products with the minimum environmental impact.

Aerosol Propellants↗
PubMed1994

The characterisation of inhalation devices by an inhalation simulator: The Electronic Lung.

The Electronic Lung is an inhalation simulator designed for the characterisation of breath-actuated inhalation devices. It enables the in-vitro evaluation of devices under conditions that have been produced in-vivo. Data generated on the Serevent Diskhaler inhaler have highlighted the reproducibility of particle size distribution of drug delivered from the device over a range of inhalation parameters.

Computer Simulation↗
PubMed1992

A reconsideration of the factors affecting birth outcome in Pakistani Muslim families in Britain.

Over recent years, Bradford has had a consistently high perinatal mortality rate (PNMR), especially amongst its Asian population, 66% of whom originate from Pakistan. There is a high incidence of consanguineous marriages reported among Pakistani and Muslim couples. Often, this observation is used to explain their higher PNMR and congenital malformation rates. The factors affecting birth outcome in Pakistani women are complex and interrelated. Socioeconomic, genetic, biological and environmental factors all contribute to adverse birth outcome. In addition, these are complicated by discrimination, communication barriers and culture blaming. The aim of this paper is to challenge midwives and other health professionals to reconsider the overwhelming emphasis placed on consanguinity as a factor affecting birth outcome, and to recognise the impact and interplay of other confounding variables.

Confounding Factors, Epidemiologic↗
PubMed1992

The pharmacokinetics of pulmonary-delivered insulin: a comparison of intratracheal and aerosol administration to the rabbit.

The pulmonary deposition and pharmacokinetics of insulin, administered via an endotracheal tube as an aerosol and instillate, in formulations containing either 113mIn-DTPA or 99mTc-DTPA (for gamma scintigraphic imaging) have been studied in four male New Zealand White rabbits. Using a randomized crossover design, the pharmacokinetics of intravenous insulin were also characterized. Recovery of immunoreactive insulin after nebulization was greater than 90%, indicating that the aerosolisation procedure did not cause appreciable insulin degradation. Gamma scintigraphy demonstrated that the penetration index (peripheral:central deposition) for the aerosolized formulation (1.52) was much greater than that for the instillate (0.32). Gamma scintigraphy also allowed exact quantification of the dose deposited after aerosol administration and thus permitted accurate determination of bioavailabilities. The bioavailable fraction for aerosolized insulin was 10-fold greater than for instilled insulin (57.2 vs 5.6%). Mucociliary clearance was likely to be greater for the instillate since it showed a preferential central deposition; this may account for the lower bioavailability. Insulin pharmacokinetics from both pulmonary formulations were absorption rate limited, resulting in postpeak half-lives which were approximately 20-fold greater than the intravenous elimination half-life (3 min). The apparent absorption rate constants resulting from instillation and aerosolisation were statistically equivalent (0.015 and 0.011 min-1, respectively). Mucociliary clearance of insulin would result in an overestimation of the true absorption rate constant; hence if mucociliary transport were greater for the instillate, then the true airways to blood transfer rate constant will be higher for the aerosolized formulation.

Aerosols↗
PubMed1992

Transfer of psychiatric inpatients: the family perspective.

Data from semistructured interviews with families of psychiatric inpatients revealed both satisfaction and dissatisfaction with hospital psychiatry professionals' practices in the course of patient transfer between units. The most significant issues were involvement of families in planning the transfer, provision of timely and adequate information to families, and availability and support of the staff. Recommendations are made for easing family stress and increasing family cooperation about the transfers.

Adult↗
PubMed1991

Diuretic effect and disposition of furosemide in cystic fibrosis.

The pharmacodynamics and kinetics of single oral and intravenous doses of furosemide were studied in 9 patients (mean age 18.5 y) with cystic fibrosis. The diuretic effect of furosemide lasted for 6 h after oral administration and 2 h following intravenous injection of the drug. The patients with cystic fibrosis had a more pronounced diuretic response both to the oral and intravenous treatments than that reported in normals. Furosemide caused a marked decrease in urine pH for 5 h following the oral dose and between the 2nd and 3rd h after i.v. injection. The baseline nocturnal urine flow rate in 7 of the 9 patients given furosemide orally was increased by 30.6% compared to that reported in healthy subjects. The bioavailability of furosemide, its mean absorption rate and the mean plasma and urinary elimination half-lives both of the oral and the intravenous drug were similar to those reported in normal subjects. The patients with cystic fibrosis showed, however, about double normal mean total clearance after both the oral and i.v. treatments, and its renal clearance was almost half the plasma clearance. Nonrenal clearance was markedly increased in the patients, which agreed with a considerable decrease in the renal excretion of the drug. The mean apparent volume of distribution was also markedly increased compared to data in the literature. Oral furosemide resulted in a moderate increase in haematocrit and haemoglobin levels in 7 of 9 patients with cystic fibrosis and marked hypokalemia developed in 6 of the 9 patients 6 h after dosing. Pulmonary function tests performed at that time were changed in an inconsistent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Flurbiprofen in post-partum women: plasma and breast milk disposition.

The plasma and milk disposition of flurbiprofen (FB) was assessed in healthy women during the early post-partum period after multiple doses of FB. The results confirmed that a pragmatic study design is an attainable requirement for definitive statements about the excretion of FB in transitional milk. Nine doses of FB (50 mg per dose) were administered during three days. Paired milk and plasma samples were obtained during this period of dosing as well as after the last dose. The plasma data were used to derive an equation, which was then used to simulate cumulative plasma profiles for multiple doses given at unequal time intervals. The observed data corresponded to the simulated cumulative profiles of FB in plasma. The plasma elimination half-life of FB during early lactation was slightly prolonged (mean 4.8 hrs) as compared to reported values for normal adult men. The peak plasma concentrations of FB were comparable to those reported for healthy volunteers. In 10 of 12 women (3-5 days post-partum) the FB concentration in breast milk was less than 0.050 micrograms/ml. In two women the milk concentrations of FB were 0.06, 0.07 and 0.07 micrograms/ml as found in only three samples. We conclude that, on the basis of dose found in milk, FB is safe for women breast feeding their infants in the early post-partum period.

Adult↗
PubMed1988

Dosage regimen of cimetidine reviewed. Possible drug accumulation after multiple oral doses.

The doses of cimetidine recommended differ in children, especially those with cystic fibrosis. These dosage regimens were derived from single-dose pharmacokinetic studies of the drug. Some authors showed, however, that after administration of repeated oral doses of cimetidine in healthy adults and children with cystic fibrosis, the elimination half-life of the drug was markedly prolonged. In view of the ability of cimetidine to inhibit metabolism of other drugs, it is suggested that the parent compound and/or it is metabolite(s) may inhibit its own metabolism during a prolonged course of treatment. Enterohepatic recirculation of the drug and/or its metabolite(s) may also contribute to prolongation of its elimination. One should therefore be cautious in using single-dose pharmacokinetic parameters to calculate repeated dose regimens and expected plasma steady-state concentrations.

Administration, Oral↗
PubMed1987

Pharmacologic factors contributing to variance in the milk to plasma ratio for acetaminophen in the goat.

A single-point estimate of the milk to plasma (M/P) drug ratio presupposes an invariant ratio. This may lead to erroneous conclusions about the amount of drug excreted in breast milk. A variance of the M/P ratio with regard to time has been shown for acetaminophen under standardized biologic conditions in the lactating goat. This ratio is potentially confounded by such factors as route of administration, dose amount and duration of exposure to the drug. Each factor was evaluated by computer simulations of the M/P ratio and by derivation of a ratio from empirical data in the goat. Route of administration was found to influence both the pattern and magnitude of the M/P ratio after acetaminophen dosing in the goat. Similar, but less, effects were found for duration of dosing. Dose itself did not influence the ratio. A temporal basis exists for each confounding factor. We thus propose that the M/P ratio is fundamentally variant with time under a standard set of biologic conditions. The contributing variance of confounding factors must be assessed if drug in milk dosing of the infant is to be accurately evaluated by use of the M/P ratio.

Acetaminophen↗
PubMed1986

High-performance liquid chromatographic determination of carbamazepine and carbamazepine 10,11-epoxide in plasma and saliva following solid-phase sample extraction.

A rapid, sensitive and simple to operate high-performance liquid chromatographic method for the simultaneous determination of carbamazepine (CBZ) and carbamazepine 10,11-epoxide (CBZ-EP) in plasma and saliva is described. The drug and its metabolite are extracted from both plasma and saliva using commercially available reversed-phase octadecylsilane bonded silica columns (Bond-Elut C18, 2.8 ml capacity). Separation of CBZ and CBZ-EP was achieved by reversed-phase chromatography, using a mobile phase consisting of acetonitrile-methanol-water (19:37:44) at a flow-rate of 1.8 ml/min in conjunction with a Nova-Pak C18 column. The analytical column, in Radial-Pak cartridge form, was used in combination with a Z-module RCSS and protected by a Guard-Pak precolumn module containing a Guard-Pak mu Bondapak C18 insert. Using ultraviolet detection at 214 nm, levels in the region of 50-100 ng/ml for CBZ and CBZ-EP can be measured with only 250 and 500 microliters of plasma and saliva, respectively. The method, which has been used to determine steady-state concentrations of the drug and its metabolite in paediatric patients receiving CBZ monotherapy, is also suitable for pharmacokinetic studies.

Carbamazepine↗
PubMed1986

Solid-phase extraction of acetazolamide from biological fluids and subsequent analysis by high-performance liquid chromatography.

A sensitive, relatively fast and simple to operate high-performance liquid chromatographic method for the determination of acetazolamide in plasma and saliva is described. Quantitative extraction of the drug from both plasma and saliva was achieved using commercially available reversed-phase octadecylsilane-bonded silica column (Bond-Elut C18, 2.8 ml capacity). Acetazolamide and the internal standard are retained on the Bond-Elut C18 column and reproducibly recovered by elution with methanol. Liquid-liquid partition chromatography, carried out on a 30-cm mu Porasil column (10-microns porous silica) using a mobile phase consisting of dichloromethane-ethanol-water-glacial acetic acid (500:65:65:1), provided adequate separation with acceptable retention times. Acetazolamide levels in the region 50-100 ng/ml can be determined in 100 microliters of plasma or 200 microliters of saliva employing ultraviolet detection at 254 nm with a sensitivity of 0.005 absorbance units full scale. Although the method is primarily used to determine steady-state drug levels in paediatric patients, its general applicability is illustrated by the 24-h plasma and saliva concentration profiles obtained from a male volunteer following oral administration of acetazolamide.

Acetazolamide↗
PubMed1986

Moving experiences: a model for inpatient transfer based on interviews with patients and their families.

Although transfer of psychiatric patients from one unit to another is a routine clinical procedure, it may constitute a crisis for patients and their families. The 61 recently transferred patients and 46 family members interviewed for this study expressed substantial dissatisfaction with the transfer process, especially with the planning and preparation stages. Based on their responses, the authors developed a model for understanding and improving inpatient transfers. The transfer process consists of four stages--planning, preparation, transfer, and adjustment--each of which presents different tasks for the patient, his family, and staff. The authors believe their transfer model is applicable to the transfer of medical inpatients and psychiatric outpatients.

Adolescent↗
PubMed1985

Improved high-performance liquid chromatographic method for the simultaneous determination of caffeine and its N-demethylated metabolites in plasma using solid-phase extraction.

An improved high-performance liquid chromatographic method for the simultaneous determination of caffeine and its N-demethylated metabolites in plasma is described. Excellent resolution of all components is provided by reversed-phase chromatography using a mobile phase consisting of 1% acetic acid-methanol (83:17) at a flow-rate of 2.7 ml/min, in conjunction with a Waters Assoc. Nova-Pak C18 column which was protected by a Waters Assoc. Guard-Pak precolumn module containing a Guard-Pak CN cartridge. Rapid extraction of caffeine and the dimethylxanthines from plasma was achieved using reversed-phase octadecylsilane bonded-silica columns (Bond-Elut C18). With only 100 microliters of sample, plasma levels in the region of 50 ng/ml for the dimethylxanthines and 100 ng/ml for caffeine can be determined using ultraviolet detection at 273 nm. The method has been used for measuring umbilical cord plasma samples to provide information regarding foetal exposure to caffeine and its metabolites and is also suitable for therapeutic drug monitoring of caffeine and theophylline levels in the treatment of neonatal apnoea.

Caffeine↗
PubMed1985

Mechanical feeding difficulties after primary repair of oesophageal atresia.

A detailed feeding questionnaire was sent to 35 sets of parents of children who had undergone successful primary repair of oesophageal atresia. Twenty-three were returned completed. All indicated difficulty with feeding. Some foods were better tolerated than others. Eighteen children had episodes of food sticking in the oesophagus, the parents using a variety of techniques to remove this. We feel that it may be possible to offer constructive, practical advice on feeding these children.

Deglutition Disorders↗
PubMed1984

Simultaneous determination of caffeine and its N-demethylated metabolites in umbilical cord plasma using high-performance liquid chromatography.

A convenient high-performance liquid chromatographic method for the simultaneous determination of caffeine and its N-demethylated metabolites in plasma is described. Separation is achieved by reversed-phase chromatography using a mobile phase consisting of 0.01 M sodium acetate buffer, pH 5.0-methanol-tetrahydrofuran (95:4:1) in conjunction with a mu Bondapak C18 column protected by a guard column containing Bondapak C18/Corasil. With a flow-rate of 3 ml/min, levels in the region of 50 ng/ml for the dimethylxanthines and 100 ng/ml for caffeine can be determined by ultraviolet detection at 254 nm. The method was used clinically for measuring cord blood samples to provide information regarding fetal exposure to caffeine and its N-demethylated metabolites during late pregnancy.

Adult↗
PubMed1984

Congenital epulis of the newborn.

A case history of congenital epulis of the newborn is described and two unusual features are noted. First, two lesions were present, and second, following excision, the patient continued to have minor feeding difficulties due to associated partial nasal obstruction.

Female↗