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Biomedical subjects

H Chrystyn

Publications and source records attributed to H Chrystyn.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1995

Pharmacokinetics of ifosfamide and its enantiomers following a single 1 h intravenous infusion of the racemate in patients with small cell lung carcinoma.

Ifosfamide is a chiral pro-drug which is administered clinically in its racemic form. Serum concentrations of rac-ifosfamide and its enantiomers were measured in 12 patients with lung carcinoma following a mean (+/- s.d.) intravenous dose of 4.2 (0.83) g infused over 1 h. The mean (+/- s.d.) volumes of distribution (VSS) of rac, (R)- and (S)-ifosfamide were 0.61 (0.17), 0.60 (0.16) and 0.61 (0.19) l kg-1, respectively. The mean (+/- s.d.) half-lives and clearances were 6.57 (1.69), 7.12 (1.92) and 5.98 (1.52) h and 0.065 (0.013), 0.060 (0.013) and 0.072 (0.014) l h-1 kg-1 for rac, (R)- and (S)-ifosfamide, respectively. The half-life of (S)-ifosfamide was significantly (P < 0.001) shorter than that of (R)-ifosfamide and it had a significantly higher clearance (P < 0.001). There was no significant difference in the volumes of distribution of the enantiomers. The clinical significance of the faster elimination of (S)-ifosfamide is not known.

Aged↗
PubMed1995

Dry powder inhalers are bioequivalent to metered-dose inhalers. A study using a new urinary albuterol (salbutamol) assay technique.

Metered-dose inhalers (MDIs) are extensively used to deliver drugs to the lungs but are driven by chlorofluorocarbon (CFC) propellants. The worldwide phasing out of CFCs within the next 5 to 10 years presents difficulties to the pharmaceutical industry. The mean +/- SD relative lung bioavailability of albuterol to the lung following inhalation of 400 micrograms of albuterol from an MDI, the Rotahaler and Diskhaler in 10 well-trained volunteers, was 2.83 (0.78), 1.72 (0.99), and 2.64 (1.23)%, respectively, expressed as a percentage of the nominal dose. The delivery of albuterol to the lungs from the MDI and Diskhaler was similar. In nine asthmatic subjects, the relative lung bioavailability of albuterol following inhalation with the MDI and Diskhaler was 1.19 (0.79) and 2.38 (1.46)%, respectively, expressed as a percentage of the nominal dose. There was no difference in reversibility 30 min after administration of the dose by the two methods. Similar lung deposition from the Diskhaler in volunteers probably is due to efficient MDI technique, which was absent in the asthmatic subjects. The Diskhaler does not rely on coordination during inhalation and therefore is easier to use.

Adult↗
PubMed1994

Enantiomeric separation of R- and S-ifosfamide and their determination in serum from clinical subjects.

A method to measure racemic, R- and S-ifosfamide concentrations from the serum of patients receiving ifosfamide chemotherapy has been developed. The racemic ifosfamide concentrations are quantified on a separate system and then the ratio of the enantiomers is determined using an achiral-chiral coupled system. Racemic ifosfamide is separated on the achiral system using a C1 spherisorb stationary phase and the eluent containing analyte is selectively transferred to the chiral system for separation of the two enantiomers by an alpha 1 glycoprotein column. On both systems the mobile phase is 1% acetonitrite in 0.015 M phosphate buffer (pH 4) at a flow-rate of 1 ml/min. The retention times of S- and R-ifosfamide were 11.6 and 13.0 mins, respectively, with a resolution factor of 1.53. Serum concentrations at least three to four half-lives post-infusion were detected by this method. In ten patients, following a mean +/- S.D. 1-h infusion of 3.9 +/- 0.32 g racemic ifosfamide, the mean +/- S.D. clearances of R- and S-ifosfamide were 0.061 +/- 0.013 and 0.072 +/- 0.014 1 h-1 kg-1.

Aged↗
PubMed1994

Ifosfamide enantiomers: pharmacokinetics in children.

Ifosfamide, like other oxazaphosphorine drugs, is chiral and there is some evidence, mainly from animal studies, of stereo-selective differences in metabolism, excretion and cytotoxic activity between the two enantiomers. The pharmacokinetics of racemic ifosfamide (RAC-IFO), R-ifosfamide (R-IFO) and S-ifosfamide (S-IFO) were studied in five children who received intravenous therapy with racemic ifosfamide on 3 consecutive days. The clearance of S-IFO was greater than that of R-IFO. The clearance value at the end of the infusion was faster than the respective rate measured at the beginning of or during the ifosfamide regimens in four children and, therefore, suggests autoinduction of elimination of both enantiomers.

Adolescent↗
PubMed1994

Volumatic usage: some generic salbutamol metered dose inhalers can be used.

BACKGROUND: The 30 minute and 24 hour post-inhalation urinary excretion of salbutamol represents the relative amount of drug deposited in the lungs and total systemic absorption, respectively. Using this method two metered dose inhalers used with a Volumatic (Allen and Hanburys Ltd, UK) large volume spacer have been compared. METHOD: Eleven healthy volunteers inhaled 4 x 100 micrograms salbutamol from either a generic salbutamol (Baker Norton, UK) or Ventolin (Allen and Hanburys Ltd, UK) metered dose inhaler with a Volumatic. The order of administration was randomised with a seven day washout period. Urine samples were collected for 0-30 minutes and then pooled up to 24 hours after inhalation. RESULTS: The mean (SD) urinary salbutamol excretion 30 minutes after inhalation with the metered dose inhalers used with the Volumatic was 22.22 (4.63) and 21.30 (5.91) micrograms for the Baker Norton and Ventolin respectively, with a mean difference (95% confidence interval (CI)) of 0.92 (-0.65 to 2.49) micrograms. Similar amounts were excreted up to 24 hours after the dose with a mean (SD) urinary excretion of 116.1 (24.3) micrograms and 114.8 (22.3) micrograms, respectively, and a mean difference (95% CI) of 1.22 (-20.39 to 22.84) micrograms. CONCLUSION: Inhalations from generic salbutamol (Baker Norton) and Ventolin metered dose inhalers with a Volumatic inhalation aid deliver similar amounts of drug to the lungs and the total systemic absorption from the two products is the same.

Administration, Inhalation↗
PubMed1994

Relative bioavailability of salbutamol to the lung following inhalation using metered dose inhalation methods and spacer devices.

BACKGROUND: Inhalation aids do not require coordination between actuation of a metered dose inhaler (MDI) with inspiration and reduce oropharyngeal impaction. The delivery of salbutamol to the lung and systemic availability following inhalation with three commonly used spacers and an open mouth technique have been evaluated using a simple noninvasive technique based on urinary excretion 30 minutes and 24 hours after the dose. METHODS: Ten healthy subjects inhaled, on randomised study days, 4 x 100 micrograms from a Ventolin MDI and, subsequently, with the aid of a Volumatic, Bricanyl Spacer, and Nebuhaler spacer device. In addition, an open mouth inhaler technique was evaluated. Urine samples were collected 0-30 minutes and 0.5-24 hours after inhalation. From these samples the relative bioavailability to the lung (urinary salbutamol excretion 30 minutes after dosing) and the systemic bioavailability of the dose (24 hour urinary excretion of salbutamol and its metabolite) for each inhalation method was obtained. RESULTS: The mean (SD) urinary excretion of salbutamol 30 minutes after inhalation using the MDI alone and with the Volumatic, Bricanyl Spacer, Nebuhaler, and open mouth technique was 2.83 (0.78)%, 3.37 (0.69)%, 4.09 (0.91)%, 4.34 (1.60)%, and 3.49 (0.98)%, respectively, expressed as a percentage of the nominal dose. The nebuhaler and Bricanyl Spacer spacer devices were found to increase the relative bioavailability of salbutamol to the lung compared with the MDI alone. Compared with the MDI the inhalation aid increases were much greater than the intra-individual variability of the urinary excretion method. In 11 individuals who each repeated the same inhalation procedure on four separate occasions, the mean (SD) coefficient of variation was 8.24 (2.36)%. The mean (SD) 24 hour urinary excretion of salbutamol and its metabolites was 26.6 (6.79), 27.0 (7.95), and 55.6 (9.74)% of the salbutamol dose for the Volumatic, Nebuhaler, and MDI, respectively. Similar values following the open mouth method and Bricanyl Spacer were 48.9 (10.97)% and 43.8 (11.57)%. These values, representing the systemic availability of the inhaled dose, were lower when inhaling with the aid of the Volumatic and Nebuhaler than inhalation from the MDI alone. CONCLUSIONS: Spacer devices improve pulmonary bioavailability of salbutamol and reduce the systemically available dose.

Administration, Inhalation↗
PubMed1993

Investigations of an optimal inhaler technique with the use of urinary salbutamol excretion as a measure of relative bioavailability to the lung.

BACKGROUND: A simple non-invasive method, in which a urine sample is taken 30 minutes after drug administration, has previously been shown to be a measure of the relative bioavailability of salbutamol to the lungs. This technique has been used to determine an optimal inhaler technique with commercially available metered dose inhalers (MDI). METHODS: Ten healthy subjects were trained in the use of MDIs. Each inhaled 4 x 100 micrograms salbutamol in a series of experiments to examine the relative bioavailability to the lung after different respiratory manoeuvres. Urine collection intervals were 0-0.5 hours and 0.5-24 hours after administration. RESULTS: There was significantly greater elimination of unchanged salbutamol 30 minutes after administration, indicating a greater relative bioavailability of salbutamol to the lungs after (1) exhaling gently to residual volume rather than to functional residual capacity before inhalation; (2) slow inhalation (10 l/min) compared with fast inhalation (50 l/min); (3) breath holding for 10 seconds after inhalation compared with no breath holding. CONCLUSIONS: All patient information leaflets and healthcare personnel should standardise the instructions given to patients and should adopt the inhalation method proposed.

Administration, Inhalation↗
PubMed1992

Measurement of the (R)- and (S)-isomers of warfarin in patients undergoing anticoagulant therapy.

An achiral/chiral high-performance liquid chromatographic system for the analysis of total warfarin together with the (R)- and (S)-enantiomers in clinical samples has been developed. The achiral analysis is achieved using a C8 column, which is coupled to a chiral stationary phase, alpha 1-acid glycoprotein (AGP), thereby allowing for analysis of warfarin isomers without interfering serum peaks. A 0.015 M phosphate buffer mobile phase with 15% v/v propan-2-ol (pH 7.0) was used on the C8/AGP system. UV analysis at 308 nm was used for quantitation of total warfarin on the C8 column and fluorescence (excitation 300 nm, emission 390 nm) detection was employed for isomer quantitation on the AGP. Retention time of total warfarin on the C8 column was 5.95 min, while that of the (S)- and (R)-warfarin on the AGP column was 10.38 and 12.69 min, respectively. Peak resolution of the warfarin isomers was 1.64. All serum samples were subjected to solid-phase extraction. Data from two patients in a single dose study indicate that a two-compartmental model could represent the warfarin concentration-time data with enterohepatic circulation. In some patients studied during steady state therapy, concentrations of (S)-warfarin were greater than (R)-warfarin indicating that the clearance of the former is slower in these patients.

Chromatography, High Pressure Liquid↗
PubMed1992

Determination of the relative bioavailability of salbutamol to the lung following inhalation.

1. The urinary excretion of salbutamol and its sulphate metabolite was measured following oral (4 mg) and inhaled (4 x 100 micrograms) administration of salbutamol. 2. Total urinary recovery of salbutamol and its sulphate conjugate indicated a mean (s.d.) relative bioavailability of 92.2 (24.8) % following inhalation compared with oral administration. 3. The mean (s.d.) elimination half-lives of salbutamol and its sulphate conjugate were 5.7 (1.4) and 4.1 (2.1) h, respectively, after oral administration and following inhalation they were 6.1 (2.1) and 5.1 (1.0) h, respectively. 4. Following oral and inhaled administration it was found that in the first 30 min the mean (s.d.) percentage of the dose excreted in the urine as unchanged salbutamol was 0.18 (0.14) and 2.06 (0.80) %, respectively (P < 0.01). The drug content of a urine sample taken 30 min after inhalation is, therefore, considered to be representative of the amount of drug delivered to the lungs. It is proposed that this method can be used to evaluate the relative bioavailability of salbutamol to the lung following inhalation by different techniques and devices.

Administration, Inhalation↗
PubMed1991

Improved bioavailability from a spironolactone beta-cyclodextrin complex.

The relative bioavailabilty of spironolactone from a complex with beta-cyclodextrin has been evaluated. Capsules containing 100 mg micronised spironolactone powder were compared with 100 mg spironolactone beta-cyclodextrin complex in 8 healthy volunteers by a single dose, double blind, crossover pharmacokinetic study. Subjects were randomly allocated to each preparation and crossed over after 2 weeks. Relative bioavailability was assessed by the measurement of serum canrenone concentrations. The mean relative bioavailability of the spironolactone cyclodextrin complex, compared to the micronised spironolactone powder, was 233%. Statistical analysis (Wilcoxon signed rank test) revealed that this difference was significant with a mean area under the serum concentration time curve of 3.90 and 1.88 mg.h.l-1 for the complex and micronised spironolactone powder, respectively. Four of the volunteer also received a 100 mg spironolactone tablet (Aldactone) under identical conditions. Pharmacokinetic analysis revealed that the mean relative bioavailability of the spironolactone beta cyclodextrin complex and micronised powder when compared with spironolactone tablets (Aldactone) was 252% and 124%, respectively. There was no change in the canrenone elimination half lives of each subject.

Adult↗
PubMed1991

The prediction of steady-state plasma phenobarbitone concentrations (following low-dose phenobarbitone) to refine its use as an indicator of compliance.

1. A model for predicting the steady-state plasma concentration of phenobarbitone following low-dose phenobarbitone used as an indicator of compliance was derived using data for 10 healthy volunteers. 2. Each volunteer was given a single 30 mg oral dose of phenobarbitone and the pharmacokinetics were described. Subsequently, volunteers were given phenobarbitone 2 mg daily for 28 days and a further pharmacokinetic profile determined during and after this period. 3. An initial predicted estimate of steady-state plasma drug concentration was made using each volunteer's demographic details. This estimate was revised by Bayesian analysis using single timed samples (24, 48, 72 or 96 h) following the single dose. 4. The model was tested on a further 10 healthy volunteers given a single 8 mg dose and who were subsequently given 2 mg daily for 28 days. 5. The revised estimate of peak steady-state plasma phenobarbitone concentration utilising the 96 h post-single dose concentration (356 ng ml-1) was least biased (mean prediction error +/- 95% CI = 10.6 +/- 19.8 ng ml-1) and most precise (root mean square error +/- 95% CI = 28.3 +/- 19.0 ng ml-1). In all cases the peak or trough steady-state drug concentration was within 13% of the predicted value. 6. The model reflected compliance accurately in a further eight volunteers with simulated partial (two-thirds) compliance. 7. The use of a predictive model using Bayesian analysis to estimate expected steady-state plasma phenobarbitone concentrations could increase further the usefulness of low-dose phenobarbitone as an indicator of compliance.

Adult↗