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Biomedical subjects

H Chrystyn

Publications and source records attributed to H Chrystyn.

At least 37 records · Page 2Linked to original sources
PubMed1999

Clinical pharmacy interventions by community pharmacists during the dispensing process.

AIMS: To evaluate the professional contact between the community pharmacist and general practitioner during the dispensing process on issues other than the legality or simple clarification of the prescription. METHODS: Fourteen community pharmacists from five adjacent localities completed details of each clinical pharmacy intervention during 1 week of each month for a period of 1 year. Each week of the month was randomly selected. When a community pharmacist had to contact the prescriber, during the dispensing of a prescription, the following data were recorded: brief patient details, the prescribed drug therapy, the reason for intervention, the outcome and the time taken. The main outcome measures were the type and nature of each intervention, the BNF category of the drug involved and the time taken. A multidisciplinary clinical panel assessed the potential of each intervention to alter the outcome of the patient's clinical management and to prevent a drug related hospital admission. These assessments were ranked between 0 and 10 (100% confident). RESULTS: During a period covering 1 week per month over 1 year, 1503 clinical pharmacy interventions were made out of 201 000 items dispensed. When normalized for the dispensing volume of each community pharmacy the lower the number of items dispensed then the greater was the percentage of interventions (P=0.013). The clinical panel decided that between 19 (0.01% of the total items dispensed) and 242 (0.12%) interventions may have prevented a drug-related hospital admission, 71 (0.04%) to 483 (0.24%) could have prevented harm whilst 103 (0.05%) to 364 (0.18%) had the potential to improve the efficacy of the intended therapeutic plan. The panel also decided that 748 (0.37%) interventions improved the clinical outcome and could have saved a visit to or by the general practitioner. Conclusion Clinical pharmacy provided by a community pharmacist during the dispensing process has the potential to provide a valuable contribution to health care.

Community Pharmacy Services↗
PubMed1999

Anatomy and physiology in delivery: can we define our targets?

Studies have shown that the receptors for beta-agonists, inflammatory markers, and mast cells are distributed throughout the airways. Thus topical delivery of drug for the management of asthma requires an even spread throughout the lungs. Particles of 2-5 microm in diameter have the greatest potential to be deposited throughout the lungs during inhalation, by impaction and sedimentation. Inhaled products, therefore, are formulated such that almost half of the dose emitted during inhalation contains particles less than 5 microm in diameter. This is known as the fine-particle dose. Studies in adults (volunteers and asthmatic patients), using radiolabeling techniques, have shown that although the amount of drug deposited in the airways (total lung dose) from different inhaled products varies, the percentages of this amount distributed throughout the central, intermediate, and peripheral zones are fairly consistent. All that varies, therefore, is the density of the spread. Studies in children indicate that lung deposition is lower than in adults. Nevertheless, all factors which affect lung deposition in adults do so also in children. The lower lung deposition in children indicates the use of adult doses, and the importance of inhaler device and of inhalation technique. The even distribution of inhaled drug throughout the required therapeutic areas highlights the importance of the total lung dose.

Administration, Inhalation↗
PubMed1999

Dry powder versus intravenous and nebulized gentamicin in cystic fibrosis and bronchiectasis. A pilot study.

Aminoglycosides are a mainstay of therapy for patients with cystic fibrosis (CF) or non-CF bronchiectasis who are infected with Pseudomonas aeruginosa (Psa). Traditionally, aerosolized antibiotics are delivered by liquid nebulization. The objective of this study was to determine whether a gentamicin dry powder inhaler (DPI) is as microbiologically active and potentially safe as gentamicin inhaled via a small-volume nebulizer (SVN) or given intravenously. The study was done according to a randomized, single-dose, and triple crossover protocol. Ten patients with CF or non-CF bronchiectasis and chronically infected with Psa were recruited. Patients received a single dose of either gentamicin 160 mg via DPI or SVN, or gentamicin at 5 mg/kg by intravenous infusion. In seven of the 10 patients, the minimum inhibitory concentration (MIC) was achieved in sputum after DPI and SVN, with mean (95% confidence interval) gentamicin concentrations at 2 h after administration of 13.1 microgram/g sputum (range: 2.2 to 23.9 microgram/g) and 97.2 microgram/g sputum (range: 0.3 to 194.2 microgram/g), respectively, whereas gentamicin levels in the sputum after intravenous administration failed to reach the MIC. Gentamicin given by DPI and SVN significantly decreased the sputum Psa density (p < 0.05), by almost one order of magnitude. No significant decline in bacterial counts was observed after intravenous gentamicin. When gentamicin was inhaled, blood concentrations were minimal, and were below concentrations known to cause systemic toxicity. For treatment of Psa infections susceptible to gentamicin, gentamicin administration by DPI appeared to be as efficient as by SVN, despite the delivery of a 7-fold lower dose to the airways.

Aerosols↗
PubMed1998

Validation of a high-performance liquid chromatography assay for urinary nedocromil sodium following oral and inhaled administration.

The validation of a solid-phase extraction and an ion pair high-performance liquid chromatographic assay for the determination of nedocromil sodium (NCS) in urine samples following oral and inhaled administration to healthy volunteers is described. NCS and its internal standard sodium cromoglycate (SCG) were extracted from urine samples using solid-phase extraction and then quantified using high-performance liquid chromatography (HPLC). A 25-cm C8 Spherisorb 5 microm stationary phase with a mobile phase containing a long alkyl chain ion-pair reagent (methanol-0.045 M phosphate buffer-0.05 M dodecyl triethyl ammonium phosphate; 550:447.6:2.4, v/v) was used. The mean (S.D.) intra-day accuracy and precision of the HPLC assay was 99.9 (1.6) and 7.05 (4.9)%, respectively. These values for the inter-day data were 102.4 (4.07) and 10.5 (2.7)%, respectively, over the concentration range investigated. The method described permits the detection of NCS in human urine at concentrations as low as 0.04 microg ml(-1) where the signal-to-noise ratio is greater than 3:1. In 10 healthy volunteers a significantly greater amount of NCS was excreted in the urine following inhalation than after oral dosing (p<0.001). The mean (S.D.) amount of NCS renally excreted at 0.5, 1.0 and 24 h following inhalation of four 2-mg doses of NCS from a metered dose inhaler (MDI) was 0.513 (0.24), 1.163 (0.49) and 4.00 (1.73)% of the nominal dose. Similar values after oral administration of 8 mg of NCS were 0.026 (0.03), 0.079 (0.06) and 0.930 (0.74)%, respectively.

Administration, Inhalation↗
PubMed1998

Determination of the relative bioavailability of nedocromil sodium to the lung following inhalation using urinary excretion.

OBJECTIVE: To determine the relative lung deposition of nedocromil sodium following inhalation by comparing the amounts of nedocromil sodium excreted in the urine after oral and inhaled dosing. METHODS: Ten healthy volunteers swallowed 8 mg of nedocromil and inhaled 4 x 2-mg doses on separate days. Urine was collected at 0.0, 0.5. 1.0, 2.0, 5.0, 24 h and 36 h after dosing. Urinary excretion of nedocromil was determined by high-performance liquid chromatography. RESULTS: A significantly greater amount of nedocromil was excreted following inhalation than after oral dosing. The mean with (SD) amount excreted at 0.5, 1.0 h and 24 h following inhalation of 4 x 2-mg doses was 41.0 (19.5), 93.0 (39.1) and 319.9 (138.1) microg. Corresponding values after oral administration of 8 mg of nedocromil were 2.1 (2.2), 6.3 (4.7) microg and 74.4 (58.8) microg, respectively. CONCLUSION: Nedocromil excreted in the urine at 0.5 h and 1.0 h after dosing is representative of the amount of drug delivered to the lungs. This method could be used to compare the relative bioavailability to the lungs following inhalation, and hence the performance of different inhaled products and inhalation techniques. The amount of nedocromil excreted in 24 h post-dose is representative of the emitted dose which was delivered to the body.

Administration, Inhalation↗
PubMed1998

The effect of dose on the characterization of aerodynamic particle-size distributions of beclomethasone dipropionate metered-dose inhalers.

The aerodynamic particle-size distribution for two doses of a Becloforte metered-dose inhaler (MDI) was measured by use of a twin-stage impinger (TSI), the new multi-stage (five-stage) liquid impinger (MSLI) and the Andersen cascade impactor (ACI) (n = 5 for each apparatus). The mean (s.d.) fine-particle doses measured by the three techniques for the Becloforte MDI were 40.3 (1.2), 45.7 (0.5) and 41.8 (0.4)% w/w, respectively; the median mass aerodynamic diameters (MMAD) measured using the MSLI and the ACI were 3.50 and 3.73 microns, respectively. The MSLI fine particle (< 6.8 microns) doses for 2, 5, 10, 20, 30 and 40 doses from Becloforte MDIs (n = 5 for each dose) were 49.7 (0.7), 52.9 (1.2), 45.3 (0.6), 45.5 (0.71), 45.9 (0.7) and 46.4 (0.7)% w/w, respectively. Values obtained using the ACI (< 5.8 microns) were 40.8 (1.0), 41.0 (0.8), 44.4 (0.5), 43.1 (0.4), 42.8 (0.5) and 40.4 (0.4)% w/w (n = 4). MMAD values measured with the MSLI were 3.39, 3.46, 3.75, 3.91, 4.15 and 4.45 microns, respectively; using the ACI they were 3.46, 3.54, 3.61, 3.66, 3.73 and 3.85 microns. The results indicate that the measured aerodynamic particle-size distributions of beclomethasone dipropionate MDIs are affected by the dose dispensed and by the apparatus used for measurement.

Administration, Inhalation↗
PubMed1997

Development and validation of an ion-pair liquid chromatographic method for the quantitation of sodium cromoglycate in urine following inhalation.

An ion-pair liquid high-performance chromatography method with solid-phase extraction for measuring urinary concentrations of sodium cromoglycate following inhalation has been developed and validated. Sodium cromoglycate was extracted from urine on a 100-mg phenyl cartridge (Isolute, Jones Chromatography) and then quantified on a 25-cm C8 Spherisorb 5 microns stationary phase with a mobile phase of methanol-0.045 M phosphate buffer-0.05 M dodecyl triethyl ammonium phosphate (550:447.6:2.4, v/v) pH 2.3, at 0.85 ml min-1 using nedocromil sodium as an internal standard and UV detection at 238 nm. The inter- and intra-day reproducibilities were 8.33 and 13.63%, respectively, at 0.25 mg l-1. The limit of determination for sodium cromoglycate was 0.25 mg l-1 (with a signal-to-noise ratio of greater than 10:1). Following oral and inhaled administration of 20 mg of sodium cromoglycate to eight healthy volunteers, the mean and S.D. of sodium cromoglycate excreted in the urine at 0.5, 1 and 24 h post-dose were 0.02, 0.05 and 0.33%, and 0.16, 0.30 and 1.55% of the dose, respectively. The urinary recovery of sodium cromoglycate at 0.5 and 1 h following inhalation can therefore be used to compare the amount of drug reaching the respiratory tract using different sodium cromoglycate inhaled products or inhalation methods.

Administration, Inhalation↗
PubMed1997

Steady-state clearance rates of warfarin and its enantiomers in therapeutically dosed patients.

Previous studies to identify the pharmacokinetics of R- and S-warfarin have not used steady-state area under the curve (AUC) data during therapeutic doses of racemic warfarin. Instead they have used high single doses of either racemic warfarin or a single enantiomer in volunteers or have taken a single blood sample from anticoagulated patients and assumed full compliance and a steady-state status. In this study, a series of steady-state racemic warfarin, R-warfarin, and S-warfarin serum concentrations, during a 24 h dosage interval, was measured in 10 compliant patients (5 females and 5 males) taking racemic warfarin. The anticoagulation status of all 10 patients according to the International Normalised Ratio (INR) was stable. Their mean (SD) age and weight were 67.0 (9.9) yr and 63.9 (15.4) kg. The mean (SD) clearances derived from steady-state AUC values, following therapeutic dosing, for racemic warfarin, R-warfarin, and S-warfarin were 2.40 (0.82), 2.30 (0.65), and 2.80 (1.17) ml/h/kg, respectively. The mean (SD) ratio of S-warfarin clearance was 1.24 (0.40). Comparison of the clearance measured from the AUC, of these patients, to one point determinations assuming steady state for the samples drawn at either 6, 15, or 20 h after dosage (during the dosing interval) showed some statistical differences. Most single point determinations of warfarin clearance assume that a sample of 12 h postdose is equivalent to that of the steady-state concentration, but in this study the steady-state concentration of only 6 patients occurred between 6 and 15 h postdate. This could explain why these studies demonstrate differences in the clearance of R- and S-warfarin compared to the values we have derived from steady-state AUC data using patients with proven compliance and therapeutic doses.

Administration, Oral↗
PubMed1997

Relative bioavailability of salbutamol to the lung following inhalation via a novel dry powder inhaler and a standard metered dose inhaler.

AIMS: The number of dry powder inhaler (DPI) devices could increase because they are easier to use than a metered dose inhaler (MDI). Using urinary excretion, the relative bioavailability of salbutamol to the lungs and the body for a prototype DPI has been compared with an MDI. METHODS: A randomized, double-blind, two way crossover study compared the amount of salbutamol in the urine 30 min following inhalation of 2 x 100 micrograms salbutamol from a prototype DPI (Innovata Biomed Ltd, UK) and a Ventolin (Allen and Hanburys Ltd, UK) MDI in 10 volunteers. The amount of salbutamol and its metabolite, the ester sulphate conjugate, renally excreted up to 24 h post inhalation was also determined to evaluate the relative bioavailability of salbutamol to the body. RESULTS: The mean (s.d.) 30 min post-treatment urinary excretion for the prototype DPI and MDI was 8.4 (2.6) and 5.0 (1.9) micrograms, respectively (P < 0.001). The total amount of salbutamol and its ester metabolite excreted in the urine over the 24 h period after inhalation was 187.9 (77.6) and 137.6 (40.0) micrograms (P < 0.05). CONCLUSIONS: The prototype DPI delivered more salbutamol to the body and the lungs than a conventional MDI. This finding supports further development of the prototype DPI. The urinary salbutamol method is able to discriminate between two different inhalation systems.

Administration, Inhalation↗
PubMed1997

Improved bioavailability and clinical response in patients with chronic liver disease following the administration of a spironolactone: beta-cyclodextrin complex.

AIMS: To compare the absorption and clinical effect of spironolactone from an inclusion complex with beta-cyclodextrin (SP-COMP) to Aldactone tablets (ALD) in chronic liver disease. METHODS: Patients, admitted with chronic liver disease, completed a randomized crossover steady state study. They received their spironolactone dose as either daily SP-COMP or ALD for 7 days. Serial blood samples were drawn over a 24 h period from day 7 of each therapy. Accurate fluid balance was recorded on days 5-7 and 12-14. Thirteen (six females) whose mean (s.d.) age and weight was 58.4(9.3) years and 74.3(19.0) kg completed the study. RESULTS: The mean (95% confidence limits) relative bioavailability for SP-COMP (compared with ALD) from steady state serum concentrations of canrenone, 6beta-hydroxyl 7alpha-thiomethyl spironolactone and 7alpha-thiomethyl spironolactone was 310.0 (265.4, 336.7), 233.4(212.9, 250.8) and 254.8(230.8, 279.0)%, respectively. Improvements in clinical status and fluid balance occurred over the last 3 days of SP-COMP with a mean (s.d.) net loss, in fluid balance, of 1370(860)ml compared with a gain of 228(936)ml during ALD. CONCLUSIONS: Better absorption of spironolactone from the spironolactone: beta-cyclodextrin complex formulation should lead to a reduction in dosage and perhaps a more consistent effect in patients with chronic liver disease.

Biological Availability↗
PubMed1997

An investigation of hospital generated pharmaceutical care when patients are discharged home from hospital.

AIMS: To investigate how seamless pharmaceutical care could be delivered. METHODS: Elderly patients discharged from hospital, to their own home, were randomized into control and study groups. Control and study group patients received the normal discharge information. The study group were also counselled about their medicines and informed about their pharmaceutical care plan. Copies of the plan were given to the study patients. All patients received a domiciliary visit between 7 and 10 days after discharge. Their current medication was compared with that on discharge and contact was made with the General Practitioner as appropriate. RESULTS: Twenty-eight study and 25 control patients with a mean (s.d.) age of 77.5 (7.3) and 77.6 (6.1) years completed the study. A pharmaceutical domiciliary visit was necessary for 21 (75%) and 24 (96%) of the study and control patients respectively. Compliance was better (P < 0.01) in the study group. Unintentional changes to the medication of 31 (14 study and 17 control) patients were found during the visit and after contact with the prescriber all but one prescription was restored to that on discharge. CONCLUSIONS: At present it is difficult to ensure seamless pharmaceutical care. A pharmaceutical domiciliary visit may be useful to ensure seamless therapeutic care and thus avoid unnecessary healthcare events and costs after a patient is discharged home.

Aged↗
PubMed1996

High-performance liquid chromatographic determination of the enantiomers of cyclophosphamide in serum.

A high-performance liquid chromatographic (HPLC) achiral-chiral coupled assay to measure the serum concentration of the enantiomers of cyclophosphamide is described. The R- and S-enantiomers of cyclophosphamide were quantified using a 5-cm-long C1 Spherisorb 5-microns column, with switching of the eluent containing racemic cyclophosphamide onto a 10-cm-long alpha 1 acid glycoprotein column. The limit of determination was 1.25 mg l-1 for each enantiomer and the ratio of the enantiomers over the range 2.5 to 100 mg l-1 was I. Serum enantiomer concentrations in blood samples taken from patients receiving 0.30 to 0.75 gm-2 of intravenous racemic cyclophosphamide could be measured at least three half-lives post dose. In six patients no significant difference in the clearance of R- and S-cyclophosphamide was found.

Antineoplastic Agents↗