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H Chrystyn

Publications and source records attributed to H Chrystyn.

At least 19 recordsLinked to original sources
PubMed2003

Dose-response relationship and reproducibility of urinary salbutamol excretion during the first 30 min after an inhalation.

AIMS: To determine the reproducibility and dose-response relationship for urinary salbutamol excretion post inhalation. METHODS: Fifteen volunteers inhaled either one, two, three, four or five doses of 100 micro g salbutamol on separate days and then seven of these also repeated each of the one, three and five doses on five occasions. After each study dose urine was collected 30 min post inhalation. RESULTS: The mean (SD) 30 min urinary salbutamol after one, two, three, four and five doses was 2.61 (1.0.), 5.47 (1.59), 8.68 (2.73), 12.34 (3.96) and 15.99 (4.50) micro g, respectively. Statistical analysis revealed a linear relationship (P < 0.001). Mean (SD) coefficient of variation after one, three and five doses was 10.5 (3.6), 10.1 (2.7) and 9.4 (2.3)%. CONCLUSIONS: The 30 min salbutamol urinary excretion post inhalation pharmacokinetic method, to compare inhaled products, is linear with inhaled dose and reproducible.

Administration, Inhalation↗
PubMed2003

Is inhalation rate important for a dry powder inhaler? Using the In-Check Dial to identify these rates.

The fraction of the emitted dose from an inhaler that has the potential to be deposited into the lungs is known as the fine particle dose (also the respirable dose). During inhalation all dry powder inhalers require a 'force' to be created inside the device so that a fine particle dose is generated from the formulation in the metering chamber. This 'force' is formed by the inhalation rate used together with the resistance (and hence design) inside an inhaler. Studies have shown that the fine particle dose is related to the clinical effect whilst other studies have reported that this dose can be dependent on the inhalation rate used. The inhalation technique recommended by the manufacturer of an inhaled device should, therefore, be used. For those dry powder inhalers that demonstrate significant flow dependent dosage emission it is important that patients use the most desirable rate that has been reported. The In-Check Dial is a simple and ease to use meter that can be used to measure the inhalation rate of a patient when they use each of the commonly prescribed inhalers that are currently available. This meter can be used to identify the most suitable inhaler for each individual.

Administration, Inhalation↗
PubMed2002

Relative lung and total systemic bioavailability following inhalation from a metered dose inhaler compared with a metered dose inhaler attached to a large volume plastic spacer and a jet nebuliser.

OBJECTIVE: To compare the lung and systemic delivery of salbutamol following inhalation from a metered dose inhaler (MDI), a MDI attached to a spacer (MDI+SP) and a nebuliser (NEB) using a urinary pharmacokinetic method. METHOD: Twelve healthy subjects each provided urine samples at 0, 30 min and pooled up to 24 h after the start of 5 x 100 microg salbutamol inhaled from MDI and MDI + SP and after 2.5 mg was delivered by NEB. Following nebulisation, the amount of salbutamol trapped on an exhalation filter together with that remaining in the apparatus was determined. The amount left in the spacer and that leaving the MDI mouthpiece was also determined. Thus, for all the methods, the amount available for inhalation from each study dose was determined. RESULTS: The mean (+/- SD) 30-min urinary excretion amounts of salbutamol for MDI, MDI+SP and NEB were 12.6+/-3.5, 27.1+/-6.0 and 16.1+/-4.6 microg, respectively. The mean ratios (90% confidence intervals) for MDI+SP compared with MDI and NEB were 230.2 (186.7, 273.8) and 183.0 (146.4, 219.7) (both P values<0.001), respectively, while that between MDI and NEB was 134 (110.4, 159.1) (P < 0.05). The mean (+/-SD) 24-h urinary excretion values for salbutamol and its metabolite were 287.0+/-46.5, 198.1+/-34.7 and 253.4+/-138.3 microg, respectively. Following inhalation a mean of 202.9+/-51.5 microg was left in the spacer. Similarly, after nebulisation 1387.7+/-88.9 microg was left in the nebuliser chamber, 26.3+/-8.0 microg in the mouthpiece and 553.8+/-68.5 microg exhaled. The mean emitted dose from the MDI was 88.4+/-6.1 microg per actuation. When normalised for the amounts available for inhalation, the mean amounts of salbutamol excreted in the urine during the first 30 min were 2.86+/-0.78, 9.15+/-1.69 and 3.06+/-0.70% following MDI, MDI + SP and NEB, respectively. CONCLUSION: Five 100-microg doses inhaled from a metered dose inhaler attached to a spacer delivered more to the lungs and less to the systemic circulation than either the same doses from a metered dose inhaler used alone or five times the dose given via a jet nebuliser. Spacers should be routinely used instead of nebulisers to manage patients unless they are short of breath.

Adult↗
PubMed2002

Determination of the relative bioavailability of salbutamol to the lungs and systemic circulation following nebulization.

AIMS: Clinical studies comparing nebulized drug delivery systems could be flawed because of the high doses used. We have compared lung and total systemic delivery of salbutamol from a nebuliser with that from a metered dose inhaler by measuring urinary recovery of drug and its sulphate metabolite. METHODS: Twelve healthy volunteers provided urine samples at 0, 0.5, 1, 2, 4, 8, 12 and 24 h after the start of dosing. Formulations and doses were 5 x 100 microg oral solution (ORAL), 5 x 100 microg from a metered dose inhaler (MDI), 2.5 mg using a nebuliser (NEB) and NEB with 25 g oral charcoal (NEBC). Each study phase was separated by 7 days and the order of dosing was randomized. RESULTS: Mean (s.d.) 30 min urinary salbutamol excretion after ORAL, MDI, NEB and NEBC was 0.4 (0.7), 12.1 (3.7), 15.0 (3.9) and 18.2 (5.7) microg, respectively (all P<0.001 compared with ORAL). When normalized for the dose available for inhalation from MDI, NEB and NEBC, the mean (s.d.) 30 min urinary excretion of salbutamol was 2.4 (0.7), 2.9 (0.6) and 2.7 (0.6)%, respectively, with a mean ratio (90% confidence interval) between NEB and NEBC, of 95.3 (91.1, 99.5)%. The mean (s.d.) excretion of salbutamol plus its metabolite over 24 h post ORAL, MDI, NEB and NEBC dosing was 297.9 (38.3), 290.3 (41.4), 266.5 (44.6) and 151.7 (40.9) microg, respectively. The mean ratio (90% confidence interval) between MDI and ORAL, and NEB and ORAL were 97.5 (94.1, 101.0) and 90.7 (81.2, 100.2)%, respectively. The NEBC data indicate that 6.07 (1.04)% of the nominal nebulized dose was delivered to the lungs. CONCLUSIONS: The 30 min urinary recovery of salbutamol, an index of the relative systemic bioavailability of salbutamol following inhalation, can be used to compare the lung deposition of nebulized systems. Similarly, the urinary 24 h recovery of salbutamol plus its metabolite, an index of the relative systemic bioavailability of salbutamol following inhalation, can be used to compare the delivery of nebulized drug to the systemic circulation.

Administration, Inhalation↗
PubMed2002

The value of inpatient pharmaceutical counselling to elderly patients prior to discharge.

AIMS: The use of medication and information discharge summaries (MIDS) has become a standard procedure in many hospitals. We have evaluated if these summaries, together with in-patient pharmaceutical counselling backed up with a simple medicine reminder card, may help with the delivery of seamless pharmaceutical care. METHODS: Elderly patients prescribed more than four items discharged to their own home received the standard discharge policy including a recently introduced MIDS and medicine reminder card. Each patient's GP was sent a copy on discharge. Pre-discharge a pharmacist counselled study patients about their medicines and compliance. A research pharmacist visited patients in their home approximately 2-3 weeks and at 3 months post-discharge to determine their drug knowledge, compliance, home medicine stocks and any healthcare related events. RESULTS: Forty-three study and 40 control patients completed both visits. Their mean (s.d.) ages were 80.2 (5,7) and 81.1 (5,8) years and they were prescribed 7.1 (1.8) and 7.1 (2.3) items, respectively. At visit 1 knowledge (P < 0.01) and compliance (P < 0.001) was better in the study group. At visit 2 compliance had improved in the study group (P < 0.001). Unplanned visits to the GP and readmission to hospital amongst the study group were 19 and 5, respectively, which were both significantly less (P < 0.05) than 27 and 13 in the control group. At visit 2 for the study group the 24 unplanned GP visits and three re-admissions were significantly (P < 0.05) less than the respective 32 and 15 in the control group. At visit 1, two study group patients had altered their own medication compared with 10 control patients. At visit 2 these reduced to 0 and 4, respectively. CONCLUSIONS: In-patient pharmaceutical counselling, linked to a medication and information discharge summary and a medicine reminder card, contributed to better drug knowledge and compliance together with reduced unplanned visits to the doctor and re-admissions. A pharmaceutical domiciliary visit consolidated the improved healthcare outcomes.

Aged↗
PubMed2002

An investigation of in vitro/in vivo correlations for salbutamol nebulized by eight systems.

The choice of a nebulized system for a patient usually depends on the equipment available. To date, there is limited guidance on the selection and use of a nebulizer. We have conducted in vitro tests described within the draft European Standard for Nebulisers (BSEN13544-1; CEN) and correlated these to in vivo pharmacokinetic performance of relative lung and systemic deposition in healthy volunteers. Eight nebulizer systems have been tested. The in vitro analysis used the recommended CEN methods to quantify the total dose available for inhalation as well as the size distribution from which the respirable dose was determined. The draft European Standard methods were slightly modified to use salbutamol rather than a fluoride tracer. For the in vivo study, nine volunteers provided urine samples after 30 min and then pooled for 24 h after the start of each nebulized dose (2.5 mg of salbutamol). Amounts of salbutamol and its metabolite excreted in the urine samples were determined. There was a significant (p = 0.02) correlation between the in vitro respirable dose and the amount of salbutamol excreted in the urine 30 min after the start of nebulization (relative bioavailability of salbutamol to the lung). Also, there was a significant (p < 0.001) correlation between the in vitro dose available for inhalation and the total amount of salbutamol and its metabolites excreted over the 24 h after the start of nebulization (relative bioavailability of salbutamol to the body). The results demonstrate that in vivo/in vitro correlations exist and warrant further investigations. The in vitro methods require further validation with in vivo correlations using patients with different severities of airway obstruction.

Aerosols↗
PubMed2001

Relative lung bioavailability of generic sodium cromoglycate inhalers used with and without a spacer device.

The relative lung bioavailability of sodium cromoglycate following inhalation has been evaluated using urinary drug excretion in nine healthly volunteers. Each inhaled four 5 mg sodium cromoglycate doses from a generic metered dose inhaler (MDI) and when it was attached to large volume spacer (MDI + VOL). A breath-actuated MDI was also evaluated either used on its own (EB) or attached to a small volume spacer tube (EBO). The mean (SD) urinary excretion of sodium cromoglycate in the first 30 min post-inhalation was 34.1 (20.2), 211.7 (123.5), 29.3 (19.5) and 52.8 (36.0) microg following MDI, MDI+VOL, EB and EBO, respectively. The cumulative mean (SD) urinary excretion of sodium cromoglycate over the 24 h post-inhalation was 364.7 (266.2), 1227.1 (459.0), 280.2 (155.4) and 429.5 (176.7) microg. A metered dose inhaler attached to a large volume spacer delivers more sodium cromoglycate to the lungs than any other inhalation method.

Administration, Inhalation↗
PubMed2001

Measurement of peak inhalation rates with an in-check meter to identify an elderly patient's ability to use a turbuhaler.

Dry powder inhalers are designed with resistance to airflow so that a respirable cloud of particles is generated during inhalation. Some of these devices require a certain inhalation rate to produce a consistent dose of respirable particles. The aim of the study was to determine the inhalation rate of elderly patients with chronic obstructive pulmonary disease (COPD) when they inhale through a Turbuhaler and assess the potential of the In-Check Meter to identify inhalation rates. Their peak inhalation rate using a normal inhalation, pre- and post-counselling, was measured using a Turbuhaler Trainer and an In-Check Meter. Spirometry was also measured. Seventy-four COPD patients with a mean (SD) age of 79.7 (8.4) years and forced expiratory volume in 1 sec (FEV1) 41.9 (12.8)% predicted. Pre-counselling 14 obtained a rate of <30 l min(-1) with the Turbuhaler Trainer, 31 from 30 to 40 min(-1), 23 between 40-60 l min(-1) and 6 > 60 l min(-1). The median (range) peak inhalation rates with the In-Check Meter were 50 (50-70), 70 (50-130), 100 (60-200) and 225 (200-250) l min(-1). Post-counselling 7, 16,41 and 10 achieved the respective peak inhalation rates using the Turbuhaler Trainer Similarly the In-Check inhalation rates were 50 (50-60), 70 (50-130), 90 (60-200) and 250 (200-270) l min(-1). The results highlight the potential of the In-Check Meter to identify patients' inhalation rates through dry powder inhalers.

Aged↗
PubMed2000

Ondansetron therapy for uremic pruritus in hemodialysis patients.

Pruritus is a distressing symptom affecting up to 90% of dialysis patients. Conventional treatment with antihistamines is often ineffective and may have unacceptable side effects. Serotonin (5-hydroxytryptamine type 3 [5-HT(3)]) is known to enhance pain perception and pruritic symptoms through receptors on sensory nerve endings. Antagonism of 5-HT(3) receptors may be of use in treating uremic pruritus. We randomly assigned 16 hemodialysis patients with persistent pruritus to treatment with the 5-HT(3)-receptor antagonist, ondansetron (8 mg), or placebo three times daily for 2 weeks each in a prospective, placebo-controlled, double-blind crossover study. Patients scored their intensity of pruritus daily on a 0-to-10 visual analogue scale (0 = no pruritus, 10 = maximal pruritus), and daily use of antihistamines as escape medication was recorded. The median daily pruritus score did not change significantly during active or placebo treatment (preondansetron, 5. 3; interquartile range [IQR], 3.4 to 6.3; during ondansetron, 3.9; IQR, 2.7 to 5.0; P = not significant; preplacebo, 3.7; IQR, 3.0 to 4. 6; during placebo, 3.6; IQR, 2.4 to 4.8; P = not significant). The median daily percentage of escape medication use decreased from 21% (IQR, 9 to 61) to 9% (IQR, 0 to 33) with ondansetron (P = not significant) and from 53% (IQR, 0 to 88) to 5% (IQR, 0 to 31) with placebo (P = not significant). There was no difference in predialysis biochemistry test results or dialysis efficacy during treatment phases. Ondansetron does not improve pruritus in hemodialysis patients. Use of antihistamines decreased with both ondansetron and placebo.

Adult↗
PubMed2000

Relative bioavailability of salbutamol to the lung following inhalation when administration is prolonged.

AIMS: Urinary salbutamol post-inhalation has been shown to be an index of lung deposition. The possibility of using the urinary method for prolonged periods of inhalation (such as nebulized therapy) has been evaluated. METHODS: On separate study days volunteers received salbutamol 5 x 100 microg via either oral administration (ORAL), oral with 5 g oral charcoal (ORAL + C), inhaled from a metered dose inhaler (MDI) or MDI plus 5 g oral charcoal (MDI + C). Each dose was separated by 2 min, i.e. administration time of 8 min. Urine samples were provided at 0, 30, 40, 60 and 120 min postdose. Also seven subjects inhaled 5x100 microg doses from the MDI on five separate occasions and provided urine 0-30 min post dose. RESULTS: No salbutamol was detected in urine samples following ORAL + C. The mean (s.d.) amounts of salbutamol excreted in the urine in the first 30 min post ORAL, MDI and MDI + C were 0.42 (0.55), 11.01 (3.77) and 11.60 (3.68) microg, respectively. The ratio of urinary salbutamol following MDI and MDI + C to ORAL in the 0-30 min collection period was 26.2 and 27.8, and between 30 and 40 min postdose was 5.1 and 4.7, respectively. There was no difference between urinary salbutamol over the first 30 min following MDI and MDI + C with a mean ratio (90% confidence interval) of 95.6 (84.0, 107.2). The mean (s.d.) coefficient of variation for the 30 min urinary salbutamol elimination following inhalation of 5 x 100 microg doses from the MDI by seven subjects (on 5 separate study days) was 9.4 (2.3)%. CONCLUSIONS: The 30 min urinary salbutamol method can be used for an inhalation period of up to 8 min to identify the relative bioavailability to the lung. Samples taken after this time period are affected by excretion of the oral absorbed fraction. Most nebulisers deliver their dose within this administration time.

Administration, Inhalation↗
PubMed2000

The relative bioavailability of salbutamol to the lung using urinary excretion following inhalation from a novel dry powder inhaler: the effect of inhalation rate and formulation.

Each dry powder inhaler has a different resistance so that a respirable dose can be generated from the formulation by the patient's inspiratory effort. It is important to recognize that this effect is achievable. The inspiratory flow characteristics of asthmatics inhaling through a Clickhaler were determined. In a separate study 10 volunteers inhaled separate 2 x 100 microg salbutamol doses from a Clickhaler (ML Laboratories plc U.K.). Two different formulations (one with a high and one with a low respirable fraction) were each inhaled using an inspiratory flow of 30 and 60 l min(-1). A urine sample was collected 30 min post inhalation and then pooled for the next 24 h. The mean (SD) inhalation rate of 24 asthmatics when they inhaled from a Clickhaler was 37.3 (14.6) l min(-1). The mean (SD) urinary salbutamol excretion during the first 30 min, by the volunteers, using the high respirable dose formulation at 30 and 60 l min(-1) was 5.59 (1.87) and 4.62 (1.49) microg respectively (P<0.01). Similar values using the low respirable dose formulation were 4.84 (1.58) and 3.86 (2.14) microg. There was no significant difference between the amounts excreted in the 24 h post-dose. The different 30-min urinary excretions following inhalation of the two formulations suggest a link between the relative bioavailability of salbutamol to the lung and the respirable dose, and that a slow inhalation rate should be used when using a Clickhaler. The patient study shows that this rate is achieved by most asthmatics without further training.

Administration, Inhalation↗
PubMed2000

Characterization of the inspiratory manoeuvre when asthmatics inhale through a Turbohaler pre- and post-counselling in a community pharmacy.

Dose emission from a Turbohaler has been shown to be dependent on the rate of inhalation, with an optimal flow of 60 l min(-1) recommended. Some patients may need counselling to achieve this fast inhalation. Inhalation rate profiles of 24 asthmatics were measured when they inhaled through a placebo Turbohaler. The setting was a community pharmacy when the asthmatics came to collect their next supply of medication. Profiles were measured before and after counselling on how to use the Turbohaler. The mean (SD) peak inhalation rate through the Turbohaler pre- and post-counselling was 48.0 (16.8) and 54.7 (17.6) l min(-1), and their inspiratory volume was 1.75 (0.68) and 1.94 (0.62) l, respectively. Their mean (SD) percent predicted FEV1 was 57.0 (18.9)%. After counselling, 12 patients achieved an inhalation rate of > 60 l min(-1) and a further four obtained > 55 l min(-1). Emphasis should be placed on counselling patients prescribed all types of inhaled devices rather than concentrating on metered dose inhalers.

Administration, Inhalation↗
PubMed1999

Relative bioavailability of sodium cromoglycate to the lung following inhalation, using urinary excretion.

AIMS: To determine if a urinary excretion method, previously described for salbutamol, could also indicate the relative bioavailability of sodium cromoglycate to the lung following inhalation from a metered dose inhaler. Method Inhaled (INH), inhaled+oral charcoal (INHC), oral (ORAL) and oral+oral charcoal (ORALC) 20 mg doses of sodium cromoglycate were given via a randomised cross-over design to 11 healthy volunteers trained on how to use a metered dose inhaler. Urine samples were collected at 0.0, 0.5, 1.0 and up to 24 h post dosing and the sodium cromoglycate urinary concentration was measured using a high performance liquid chromatographic method. RESULTS: No sodium cromoglycate was detected in the urine up to 24 h following ORALC dosing. A mean (s.d.) of 3.6 (4.3) microg, 10.4 (10.9) microg and 83.7 (71.1) microg of the ORAL dose was excreted, in the urine, during the 0.5, 1.0 and 24 h post dose collection periods, respectively. Following INH dosing, the renal excretion was significantly higher (P<0.01) with 32.9 (14.5) microg, 61.2 (28.3) microg and 305.6 (82.3) microg excreted, respectively. The SCG excreted at 0.5, 1.0 and 24 h collection periods following INHC dosing were 26.3 (8.4) microg, 49.3 (18.1) microg and 184.9 (98.4) microg, respectively. There was no significant difference between the excretion rate of sodium cromoglycate following INHC when compared with INH dosing in the first 0.5 and 1.0 h. CONCLUSIONS: The urinary excretion of sodium cromoglycate in the first 0.5 h post inhalation can be used to compare the relative lung deposition of two inhaled products or of the same product using different inhalation techniques. This represents the relative bioavailability of sodium cromoglycate to the lung following inhalation. Similar 24 h urinary excretion of sodium cromoglycate can be use to compare the total dose delivered to the body from two different inhalation products/inhalation methods. This represents the relative bioavailability of sodium cromoglycate to the body following inhalation. Because of the lack of difference between the INH and INHC in the first 0.5 h, the use of activated charcoal is not necessary when this method is used to compare the relative lung bioavailability of different products or techniques.

Administration, Inhalation↗
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↗