bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the effects of nadolol and bisoprolol on noradrenaline‐evoked venoconstriction in man in vivo
Authors: Abdelmawla A. H. , Langley R. W. , Szabadi E. , Bradshaw C. M. 
Published: March 2003

Aims
In an attempt to explore the possible involvement of venodilator β‐adrenoceptors in the constrictor response of the human dorsal hand vein to noradrenaline, we examined the ability of nadolol, a non‐selective β1/β2‐adrenoceptor antagonist, and bisoprolol a selective β1‐adrenoceptor antagonist, to potentiate the response.
Methods
Twelve healthy male volunteers participated in three weekly sessions. In each session nadolol (40 mg), bisoprolol (5 mg) or placebo was ingested, and (‐) noradrenaline acid tartrate (0.33–33.33 ng min−1 ) was infused locally into the dorsal hand vein 2 h after the ingestion of the drugs. Changes in vein diameter were monitored with the dorsal hand vein compliance technique. Subjects were allocated to treatments and sessions according to a double‐blind balanced cross‐over design. Systolic and diastolic blood pressure, and heart rate were also measured.
Results
Noradrenaline produced dose‐dependent venoconstriction which was antagonized by bisoprolol but remained unaffected by nadolol (ANOVA with repeated measures: F(2,22)=5.07, P<0.025; Dunnett's test: placebo vs nadolol; t=0.35, df=22, k=3, NS; placebo vs bisoprolol; t=2.83, df=22, k=3, P<0.01 ). Mean (±s.e. mean) log ED50s (ng min−1 ) were 0.44±0.15 (placebo), 0.73±0.11 (bisoprolol) and 0.50±0.21 (nadolol); mean (95% CI) differences were 0.29 (−0.005, 0.58) for placebo vs bisoprolol and 0.06 (−0.35, 0.46) for placebo vs nadolol. Both active drugs significantly (compared with placebo, P<0.05) decreased (mean change from pretreatment±s.e. mean) heart rate (bisoprolol −16.08±2.01; nadolol −11.67±2.06) and systolic blood pressure (bisoprolol −15.0±0.80; nadolol −9.47±0.18).
Conclusions
The failure of nadolol and bisoprolol to potentiate noradrenaline‐evoked venoconstriction argues against the involvement of masked venodilator β‐adrenoceptors in the response. The mechanism underlying the antagonism of noradrenaline‐evoked venoconstriction by bisoprolol remains to be elucidated.
Lacidipine: effects on vascular pressor responses throughout the dosage interval in normotensive subjects
Authors: Ueda Shinichiro , Donnelly Richard , Panfilov Vsevolod , Morris Andrew D. , Elliott Henry L. 
Published: March 2003

Aims
To assess the duration and consistency of the pharmacological activity of the dihydropyridine calcium antagonist drug, lacidipine.
Methods
Eight healthy normotensive young males participated in a double‐blind randomised crossover comparison of single and multiple doses (for 2 weeks) of lacidipine and placebo. The calcium antagonist effects were quantified at 2, 6 and 24 h post dose by the extent of the attenuation of the pressor responses to the intravenous administration of the vasoconstrictors angiotensin II and noradrenaline.
Results
After 2 weeks of treatment, lacidipine consistently and significantly attenuated the pressor responses to both agents at 2 h post dose. At 6 and 24 h post dose there was a significant and progressive decline in the effectiveness of lacidipine in attenuating the pressor responses and for the response to angiotensin II there was no statistically significant effect at either 6 or 24 h post dose.
Conclusions
These results indicate that there is an obvious ‘peak’ in the pharmacological activity of lacidipine at about 2 h post dose and that this activity is not fully and consistently maintained throughout 24 h.
Prescription patterns of diuretics in Dutch community‐dwelling elderly patients
Authors: Van Kraaij Dave J. W. , Jansen René W. M. M. , De Gier Johan J. , Gribnau Frank W. J. , Hoefnagels Willibrord H. L. 
Published: March 2003

Aims
To describe age‐ and gender‐related prescription patterns of diuretics in community‐dwelling elderly, and to compare diuretics to other cardiovascular (CV) medications.
Methods
Cross‐sectional study of patient‐specific prescription data derived from a panel of 10 Dutch community pharmacies. Determination of proportional prescription rates and prescribed daily dose (PDD) of diuretics, cardiac glycosides, nitrates, angiotensin converting enzyme (ACE) inhibitors, β‐adrenoceptor blockers, and calcium channel blockers in all 5326 patients aged 65 years or older dispensed CV medications between August 1st, 1995 and February 1st, 1996.
Results
Diuretics were prescribed to 2677 of 5326 patients (50.3%), 1325 patients (24.9%) using thiazides and 1198 patients (22.5%) using loop diuretics. Prescription rates of loop diuretics increased from 15.1% in patients aged 65–74 years to 37.2% in patients aged 85 years or older. Rates also increased for digoxin and nitrates. Rates for thiazide diuretics remained unchanged with age; rates for β‐adrenoceptor blockers, ACE inhibitors and calcium channel blockers declined with age. Thiazides were prescribed to 30.1% of women compared with 16% of men (P<0.001). Average PDD was 135±117% of defined daily dose (DDD) for loop diuretics, and highest for bumetanide (245±2.01% of DDD, equivalent to 2.5±2.0 mg). Average PDD was 74±40% of DDD for thiazides, and highest for chlorthalidone (100±49% of DDD, equivalent to 25±12 mg).
Conclusions
Important characteristics of diuretic usage patterns in this elderly population were a steep increase in loop diuretic use in the oldest old, a large gender difference for thiazide use, and high prescribed doses for thiazides.
Pain‐mediated altered absorption and metabolism of ibuprofen: an explanation for decreased serum enantiomer concentration after dental surgery
Authors: Jamali Fakhreddin , Kunz‐Dober Cornelia M. 
Published: March 2003

Aims Rapid onset of analgesia is essential in the treatment of acute pain. There is evidence that conditions of stress cause delayed and decreased pain relief from oral analgesic products through impaired absorption. The aim was to determine the effect of surgery for removal of wisdom teeth on the plasma concentration‐time profile of ibuprofen enantiomers.Methods Racemic ibuprofen, 200 mg in one group (n=7) and 600 mg in another group (n=7) was administered 1 week before (control) and again after (test) surgical removal of wisdom teeth. Serum concentrations of ibuprofen enantiomers were measured for 6 h.Results During the control phase, S‐ and R‐ibuprofen concentrations were within the suggested therapeutic range. Surgery resulted in a 2 h delay in the mean time to peak concentration, significant decreases in serum ibuprofen concentration following both doses, and a fall to sub‐optimal serum concentrations following the 200 mg dose. During the first 2 h after the 200 mg dose, dental extraction resulted in a significant reduction of the area under serum drug concentration (AUC (0, 2 h) mg l−1 h) from 5.6±2.9 to 1.6±1.8 (P<0.01) and from 5.5±3.0 to 2.1±2.0 (P<0.05) for S and R‐ibuprofen, respectively. Similar observations were made following the 600 mg dose for AUC (0, 2 h) of S‐ibuprofen (from 14.2±6.1 to 7.2±5.5 mg l−1 h, P<0.05) with no significant difference for R‐ibuprofen (from 14.4±9.5 to 5.8±7.1). AUC (0, 6 h) was also significantly reduced by surgery. The pattern of stereoselectivity in serum ibuprofen concentration was reversed by surgery such that the S enantiomer was predominant in the control phase but not in the post‐surgery phase, which is suggestive of reduced metabolic chiral inversion.Conclusions Surgery for wisdom tooth removal resulted in substantial decreases in the serum concentration of ibuprofen enantiomers and a prolongation in the time to peak concentration. Reduced absorption and altered metabolism are the likely cause of these changes. Thus, dental patients may experience a delayed response and possible treatment failure when taking ibuprofen for pain relief after surgery. Our observation may have implications for the treatment of other diseases.
A pharmacokinetic model for alpha interferon administered subcutaneously
Authors: Chatelut Etienne , Rostaing Lionel , Grégoire Nicolas , Payen Jean‐Louis , Pujol André , Izopet Jacques , Houin Georges , Canal Pierre 
Published: March 2003

Aims To model the pharmacokinetic profiles of alpha interferon (αIFN) after a single subcutaneous (s.c.) injection of 3 million units of alpha 2b interferon, to correlate the pharmacokinetic parameters with patient demographic covariates, and to develop a limiting sampling strategy for determining the αIFN plasma area under the curve of concentration vs time (AUC).Methods The plasma αIFN pharmacokinetics were determined in 27 patients with chronic hepatitis C virus infection after the first s.c. injection of the drug. Ten patients had normal renal function and 17 were chronic haemodialysis patients. Plasma samples were assayed by an Elisa method. Concentration‐time data was analysed by a population approach using NONMEM.Results The pharmacokinetic model which better described the concentration vs time data was a one‐compartment model with two processes of absorption: a zero‐order followed by a first‐order process. The mean clearance of dialysis patients represented 37% (with 95% confidence interval: 30%–44%) of the mean value of the patients with normal renal function. The volume of distribution was significantly correlated to the body surface area. Bayesian analysis using NONMEM allowed determination of the individual plasma AUC from three samples within the 24 h period post s.c. injection.Conclusions The present pharmacokinetic model will allow one to obtain individual parameters such as, the area under the curve of concentration vs time from a limited‐sampling strategy, and to perform pharmacokinetic‐pharmacodynamic analysis of combined αIFN plasma concentrations and viraemic data.
Dietary caffeine as a probe agent for assessment of cytochrome P4501A2 activity in random urine samples
Authors: Nordmark Anna , Lundgren Stefan , Cnattingius Sven , Rane Anders 
Published: March 2003

Aims To validate the use of randomly collected urine samples for assessment of cytochrome P4501A2 (CYP1A2) activity based on dietary caffeine (caffeine metabolic ratio, MRcaff ), and to relate the MRcaff to caffeine intake and smoking habits in a larger group of individuals.Methods Nineteen healthy volunteers were included in the validation study. Caffeine (100 mg) was ingested and a urine sample was collected after 6 h. Within the following week a random urine sample was collected in the individuals without a preceding test dose of caffeine. Urine samples were analysed for caffeine and its metabolites by h.p.l.c. and the (AFMU+1U+1X)/1,7U metabolic ratio was used to reflect CYP1A2 activity. In an extended investigation of 522 healthy pregnant women the MRcaff was related to intake of caffeine from various sources, and to smoking.Results The results from the random and standardised sampling methods correlate with each other (correlation coefficient of MRcaff was 0.91). The MRcaff as assessed by the random sampling method in a larger population was not affected by source or amount of caffeine ingested. Significantly higher MRcaff was found in smokers compared to non‐smokers. In the large group of individuals the random sampling method was possible to use in 80% of the cases. In the residual 20% one or several of the metabolite concentrations were too low or unmeasurable.Conclusions Our study demonstrates that the random urine caffeine phenotyping method is possible to use in as many as 80% of the individuals when based on dietary caffeine. Our approach should prove applicable in most countries with widely spread caffeine consumption. The method is useful in larger studies of drug metabolising enzyme activities and minimises the time consumption and costs.
Apparent autoinduction of valproate β‐oxidation in humans
Authors: McLaughlin Daniel B. , Andrews Jaymie A. , Hooper Wayne D. , Cannell Graeme R. , Eadie Mervyn J. , Dickinson Ronald G. 
Published: March 2003

Aims  The study aimed to show whether autoinduction of valproate (VPA) along its β‐oxidation pathway occurred upon chronic dosing in humans.Methods  Twelve young volunteers without active illness took sodium valproate (NaVPA) 200 mg orally 12 hourly for 3 weeks. On days 7 and 21, serial blood samples and all urine passed over an interdosing interval from 08.00 to 20.00 h were collected for analysis of VPA and certain metabolites.Results  Plasma AUC(0,12 h) of VPA was significantly lower on day 21 than on day 7 (2.40 vs 2.84 µmol ml−1 h, 95% CI for the difference 0.13–0.81 µmol ml−1 h). Significant differences in plasma AUC(0,12 h) of the β‐oxidation metabolites E‐2‐en‐VPA and 3‐oxo‐VPA were not found. However, formation clearances of plasma VPA to urinary E‐2‐en‐VPA and 3‐oxo‐VPA were significantly increased from day 7 to day 21 (0.010 vs 0.024 and 2.57 vs 3.60 ml kg−1 h−1, respectively, 95% CI for the differences −0.025 to −0.004 and −1.72 to −0.34 ml kg−1 h−1, respectively). Formation clearances to VPA‐glucuronide (0.534 vs 0.505 ml kg−1 h−1) and 4‐OH‐VPA (0.112 vs 0.110 ml kg−1 h−1) were not significantly different.Conclusions  Regular low dose VPA intake in humans over a period of 3 weeks appears to be associated with a small induction of its metabolism by the β‐oxidation pathway, but not by glucuronidation or 4‐hydroxylation.
Feasibility study of multicentre comparison of NHS hospital pharmacy computer data
Authors: Walker Pauline Debra , Walley Tom 
Published: March 2003

Aims
This study aims to determine the feasibility of collecting, collating and analysing drug expenditure data from a sample of acute hospitals in England.
Methods
The hospital pharmacy computer system was used to report on drug expenditure from 16 hospitals throughout England for a 2 year period. These data were analysed as a whole and hospital episode statistics were correlated to hospital drug costs.
Results
Hospital outpatient costs were found to be approximately one third of hospital inpatient costs. Cardiovascular drugs accounted for the greatest increase in expenditure for both inpatients and outpatients (25%). The most expensive therapeutic area of drug use across all sites was anti‐infectives. The average daily number of occupied beds explained 55% of the variation in inpatient expenditure and the number of outpatient (including Accident and Emergency) attendances explained 60% of the outpatient drug expenditure.
Conclusions
This project has confirmed the feasibility of collecting, collating and analysing hospital drug expenditure and identified some interesting patterns and trends in hospital drug use. Hospital activity is reflected in hospital drug costs.
First trimester exposure to cefuroxime: a prospective cohort study
Authors: Berkovitch Matitiahu , Segal‐Socher Idit , Greenberg Revital , Bulkowshtein Mordechai , Arnon Judy , Merlob Paul , Or‐Noy Asher 
Published: March 2003

Aims
There are no published studies on the safety of cefuroxime use during pregnancy. We therefore investigated prospectively the possible teratogenic effect of intrauterine exposure to cefuroxime.
Methods
One hundred and six women who received cefuroxime during the first trimester of pregnancy were recruited from three teratogen information centres in Israel. Exposed women were paired for age, smoking habits and alcohol consumption with references being exposed to nonteratogenic antibiotics administered for the same indications.
Results
Maternal history, birthweight, gestational age at delivery, rates of live births, spontaneous abortions and fetal distress were comparable among the two groups. Rates of major malformations in the cefuroxime group (3.2%) did not differ from references (2%) (P = 0.61, relative risk = 1.56, 95% confidence interval 0.27–9.15). There was a significantly higher rate of induced abortions among the cefuroxime exposed women as compared to the references (P = 0.04, relative risk = 3.33, 95% confidence interval 0.94–11.77).
Conclusions
Our data may suggest that exposure to cefuroxime during the first trimester is probably not associated with an increased risk for malformations or spontaneous abortions; however, in light of the small sample size and the broad confidence limits, larger studies are needed to confirm these findings.
The pharmacokinetics and pharmacodynamics of oral dofetilide after twice daily and three times daily dosing
Authors: Allen Michael J. , Nichols Donald J. , Oliver Stuart D. 
Published: March 2003

Aims
The pharmacokinetics and pharmacodynamics of oral dofetilide, a novel, class III antiarrhythmic drug, were assessed during administration either twice or three times daily.
Methods
Dofetilide was administered orally to three groups of healthy subjects in daily doses of 1000 µg (n = 8), 1500 µg (n = 8), or 2500 µg (n = 9) as twice daily and three times daily treatment regimens, with the two regimens assigned randomly as a two‐way crossover for each subject and separated by at least a 6 day washout period.
Results
Pharmacokinetic analysis indicated a rise in plasma dofetilide concentrations until steady state was attained on day 3. Ctrough had a linear dependence on dose for both the twice daily and three times daily dosing regimens. The maximum concentration attained (Cmax) and the area under the concentration vs time curve (AUC(0,τ) increased linearly with dose for each dosing regimen on both days 1 and 5 of dosing. Cmax occurred at 2 h. Pharmacodynamic measurements showed that the QTc interval increased in a dose‐dependent manner and that the time to maximum QTc was 2 h after dosing. A linear relationship was determined between plasma dofetilide concentration and the prolongation of the QTc interval. The slope of this line was significantly greater on day 1 (ranging from 12.9 to 14.2 ms/ng ml−1) than on day 5 (ranging from 9.9 to 12.8 ms/ng ml−1).
Conclusions
The pharmacokinetics and pharmacodynamics of dofetilide are predictable and based on a linear relationship for both twice daily and three times daily dosing regimens. The QT responsiveness to dofetilide is greater on day 1 than on day 5.
Reducing electrostatic charge on spacer devices and bronchodilator response
Authors: Wildhaber Johannes H. , Waterer Grant W. , Hall Graham L. , Summers Quentin A. 
Published: March 2003

Aims
Plastic spacers are widely used with pressurized metered dose inhalers (pMDI). Reducing electrostatic charge by washing spacers with detergent has been shown to greatly improve in vitro and in vivo drug delivery. We assessed whether this finding is associated with an improved bronchodilator response in adult asthmatics.
Methods
Twenty subjects (age 18–65 years) with a known bronchodilator response inhaled in random order salbutamol from a pMDI (Ventolin®) through an untreated new spacer (Volumatic®) and through a detergent washed spacer. Patients received the following doses of salbutamol via pMDI at 20 min intervals: 100 µg, 100 µg, 200 µg, 400 µg, 800 µg. Spirometry, heart rate and blood pressure were checked prior to each dose and 20 min after the last dose.
Results
There were no differences between baseline forced expiratory volume in 1 s (FEV1) using either spacer (2.61 ± 0.56 and 2.52 ± 0.45 l, untreated and treated with detergent, respectively; mean ± s.d.). The provocation dose required to cause a clinically significant improvement of 10% in FEV1 (PD10) was significantly lower when the detergent treated spacer was used (1505 ± 1335 and 430 ± 732 µg, untreated and treated, respectively, P < 0.002).
Conclusions
We have demonstrated an improvement in bronchodilator response, in adult asthmatics, after reducing the electrostatic charge in a spacer device by washing it with ordinary household detergent. This finding stresses the importance of an optimal choice of delivery device for asthma medication.
Quinapril and its metabolite quinaprilat in human milk
Authors: Begg E. J. , Robson R. A. , Gardiner S. J. , Hudson L. J. , Reece P. A. , Olson S. C. , Posvar E. L. , Sedman A. J. 
Published: March 2003

Aims  To measure the milk to plasma ratio (M/P) of quinapril and its active metabolite quinaprilat in lactating mothers and to assess likely infant exposure.Methods  A single dose of quinapril 20 mg was administered to six healthy mothers who had been breastfeeding their infants for at least 2 weeks. Blood was sampled for the measurement of quinapril and quinaprilat at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h. Milk was collected for measurement of quinapril and quinaprilat concentrations over the periods −4–0, 0–4, 4–8, 8–12, 12–18, 18–24 h. The areas under the plasma and milk concentration‐time curves were estimated and an M/P ratio derived for both quinapril and quinaprilat.Results  The M/P ratio for quinapril was 0.12 (95% CI 0.09,0.14). No quinapril was detected in milk after 4 h. No quinaprilat was detected in any of the milk samples. The estimated ‘dose’ of quinapril that would be received by the infant was 1.6% (95% CI 1.0,2.2) of the maternal dose, adjusted for respective weights.Conclusions  Quinapril appears to be ‘safe’ during breastfeeding according to conventional criteria, although as always, the risk:benefit ratio should be considered when it is to be given to a nursing mother.
Drug expenditure in hospitals: what do German ward physicians know?
Authors: Schnurrer J. U. , Stichtenoth D. O. , Troost R. , Frölich J. C. 
Published: March 2003

Aims
Ward physicians hold key positions in the course of efforts to reduce drug expenditures in hospitals. This study evaluated the knowledge of German hospital physicians with respect to the daily therapeutic costs of 21 frequently used drugs.
Methods
A questionnaire survey was carried out among 168 ward physicians from university and municipal hospital departments of internal medicine.
Results
One hundred and twenty‐seven physicians returned a completed questionnaire, a response rate of 75.6%. On average the physicians successfully identified both low cost and expensive drugs. The prices of inexpensive and moderately expensive drugs were generally overestimated whereas those for the expensive and highly expensive drugs were underestimated in 35% and 68% of respondents, respectively.
Conclusions
The results of this survey of German hospital physicians suggest that a more economically efficient use of drugs could be achieved by an improved knowledge of daily therapeutic costs.
A randomized controlled assessment of the effects of different dosing regimens of budesonide on the HPA‐axis in healthy subjects
Authors: Andersson Norma , Källén Anders , Thorsson Lars 
Published: March 2003

Aims  To investigate the effect on the hypothalamo‐pituitary‐adrenal (HPA) axis of treatment with budesonide, 400 µg once daily, morning or evening, or 200 µg twice daily, and 800 µg twice daily via Turbuhaler in a randomized, placebo‐controlled, double‐blind, double‐dummy crossover study.Methods  Healthy men received budesonide, 400 µg in the morning (08.00–09.00 h) or evening (20.00–21.00 h), budesonide, 200 µg twice daily, 800 µg twice daily, and placebo twice daily, for 1 week each. Plasma and urine samples were obtained over 24 h on day 7 for cortisol determination. Twenty‐five subjects completed all treatments, and 27 were included in the analysis.Results  The 24 h plasma cortisol concentrations vs placebo (95% CI) were 98% (89, 108) for 400 µg in the morning, 92% (83, 100) for 400 µg in the evening, 95% (86, 104) for 200 µg twice daily, and 76% (70, 84) for 800 µg twice daily.Conclusions  Budesonide at a dose of 400 µg day−1 via Turbuhaler had no statistically significant effect on 24 h cortisol production, irrespective of whether treatment is given once or twice daily, whereas a dose of 800 µg twice daily resulted in a statistically significant suppression vs placebo. Neither could a significant difference be found between morning and evening dosing.