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P Lundborg

Publications and source records attributed to P Lundborg.

At least 19 recordsLinked to original sources
PubMed2003

Review article: Esomeprazole--enhanced bio-availability, specificity for the proton pump and inhibition of acid secretion.

Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor available for clinical use as a single isomer. It demonstrates pharmacological and clinical benefits beyond those seen with the racemic omeprazole. Esomeprazole has higher and more consistent bio-availability than omeprazole, which results in a greater area under the plasma concentration-time curve. It is the area under the plasma concentration-time curve of omeprazole and esomeprazole that determines how much of each reaches the parietal cell, and thus the control of gastric acid secretion that is achieved. Esomeprazole, like other proton pump inhibitors, has a high specificity for the acidic environment of the parietal cell, where it is accumulated, activated and covalently inhibits the proton pump. Proton pumps elsewhere in the body do not achieve the level of acidity needed for accumulation and activation. Esomeprazole, 40 mg once daily, provides more effective control of gastric acid secretion than omeprazole, 20 or 40 mg once daily, and all other proton pump inhibitors given at their standard doses. This translates into greater clinical effect compared with omeprazole, 20 mg once daily, and lansoprazole, 30 mg once daily, in the management of reflux disease. Esomeprazole therapy is well tolerated, with a low adverse events profile, similar to that seen with omeprazole.

Anti-Ulcer Agents↗
PubMed2001

Safety and efficacy of long term esomeprazole therapy in patients with healed erosive oesophagitis.

OBJECTIVE: To evaluate the safety and tolerability of long term treatment with esomeprazole in patients with healed erosive oesophagitis, and to describe its efficacy in the maintenance of healing. DESIGN AND SETTING: US multicentre, noncomparative, nonblind study. PATIENTS AND PARTICIPANTS: 807 patients with endoscopically confirmed healed erosive oesophagitis. METHODS: Patients received esomeprazole 40 mg once daily for up to 12 months. Adverse events and clinical laboratory tests were assessed over the study period. Endoscopy was performed at the final visit of the antecedent healing trials and at months 6 and 12 of the current safety trial; gastric biopsies were obtained at the initial visit of the healing trials and at the end of the safety trial. RESULTS: 80.9% of patients completed 6 months of treatment; 76.6% completed 12 months of treatment. There were no serious drug-related adverse events. Diarrhoea, abdominal pain, flatulence, and headache were the only treatment-related adverse events reported by >3% of patients. Mean changes in laboratory measures were generally small and not clinically meaningful. Plasma gastrin levels increased, as expected, and reached a plateau after 3 months. No changes in gastric histological scores were noted in the majority of patients. Evaluation of gastric biopsies revealed an overall decline in chronic inflammation and atrophy. Intestinal metaplasia findings remained essentially unchanged. Life table estimates of maintenance of healing were 93.7% [95% confidence interval (CI) 92.0 to 95.5%] at 6 months and 89.4% (95% CI 87.0 to 91.7%) at 12 months. CONCLUSIONS: Daily treatment with esomeprazole 40 mg for up to 1 year in patients with healed erosive oesophagitis was generally well tolerated and effective. No safety concerns arose.

Adolescent↗
PubMed2000

Omeprazole for treatment of chronic erosive esophagitis in children: a multicenter study of efficacy, safety, tolerability and dose requirements. International Pediatric Omeprazole Study Group.

OBJECTIVES: To determine the efficacy, safety, and tolerability of omeprazole in children and to determine the doses required to heal chronic, severe esophagitis. STUDY DESIGN: Open multicenter study in children aged 1 to 16 years with erosive reflux esophagitis. The healing dose of omeprazole used was that with which the duration of acid reflux was <6% of a 24-hour intraesophageal pH study. Follow-up endoscopy was performed after 3 months of treatment with the healing dose. RESULTS: At entry, two thirds of 57 patients who completed the study had esophagitis grade 3 or 4 (scale 0-4); some 50% had neurologic impairment or repaired esophageal atresia. Of the 57 patients, 54 healed; 3 did not heal and left the study, and 3 healed with a second course. Doses required for healing were 0.7 to 3.5 mg/kg/d: 0.7 mg/kg/d in 44% of patients and 1.4 mg/kg/d in another 28%. Healing dose correlated with grade of esophagitis but not with age or underlying disease. Reflux symptoms improved dramatically in almost all of the 57 patients, including the unhealed patients. CONCLUSIONS: Omeprazole is well tolerated, highly effective, and safe for treatment of erosive esophagitis and symptoms of gastroesophageal reflux in children, including children in whom antireflux surgery or other medical therapy has failed. On a per-kilogram basis, the doses of omeprazole required to heal erosive esophagitis are much greater than those required for adults.

Adolescent↗
PubMed2000

Pharmacokinetics of orally administered omeprazole in children. International Pediatric Omeprazole Pharmacokinetic Group.

OBJECTIVES: The aim of this study was to examine the pharmacokinetics of orally administered omeprazole in children. METHODS: Plasma concentrations of omeprazole were measured at steady state over a 6-h period after administration of the drug. Patients were a subset of those in a multicenter study to determine the dose, safety, efficacy, and tolerability of omeprazole in the treatment of erosive reflux esophagitis in children. Children were 1-16 yr of age, with erosive esophagitis and pathological acid reflux on 24 h-intraesophageal pH study. The "healing dose" of omeprazole was that at which subsequent intraesophageal pH study normalized. Children remained on this dose for 3 months, and during this period the pharmacokinetics were measured. RESULTS: A total of 57 children were enrolled in the overall healing phase of the study. Pharmacokinetic study was optional for subjects and was performed in 25 of the 57 enrolled. The doses of omeprazole required were substantially higher doses per kilogram of body weight than in adults. Values of the pharmacokinetic parameters of omeprazole were generally within the ranges previously reported in adults. However, the plasma levels, area under the plasma concentration versus time curve (AUC), plasma half-life (t(1/2)), and maximal plasma concentration (Cmax), were lower in the younger age group, when the AUC and Cmax were normalized to a dose of 1 mg/kg. Furthermore, within the group as a whole, these values showed a gradation from lowest in the children 1-6 yr of age to higher in the older age groups. CONCLUSIONS: The pharmacokinetics of omeprazole in children showed a trend toward higher metabolic capacity with decreasing age, being highest at 1-6 yr of age. This may explain the need for higher doses of omeprazole on a per kilogram basis, not only in children overall compared with adults but, in many cases, particularly in younger children.

Administration, Oral↗
PubMed1998

Helicobacter pylori serology in elderly people: a 21-year cohort comparison in 70-year-olds and a 20-year longitudinal population study in 70-90-year-olds.

AIMS: (i) to compare Helicobacter pylori serology in two 70-year-old cohorts in Gothenburg, Sweden, born 21 years apart, (ii) to study H. pylori serology in a 70-year-old cohort over 20 years. POPULATION AND METHOD: H. pylori serology at the age of 70 was investigated in 98 men and 132 women born in 1901/02 and in 77 men and 113 women born in 1922. In 21 men and 40 women Helicobacter serology was monitored longitudinally with examinations at 70, 81, and 90 years of age. The analyses were performed on frozen samples by use of an in-house enzyme immunoassay with a sensitivity of 0.99, specificity of 1.00 and positive and negative predictive values of 0.96 and 1.00, respectively. Absorbance values <0.500 were interpreted as negative; values of > or = 0.700 were interpreted as positive, and values in between as inconclusive. RESULTS: The 70-year-old cohort, born in 1922, showed a significantly lower proportion of subjects with positive H. pylori serology in both men (57.1% vs 80.6%) and women (48.7% vs 75.8%) compared with 70-year-olds born in 1901/02. There were no significant sex differences in either cohort. No longitudinal increase or decrease could be demonstrated in those who were examined at 70, 81 and 90 years of age. CONCLUSIONS: The difference in H. pylori prevalence between the two cohorts may reflect a rapid change in socio-economic conditions in Sweden during this 20-year period.

Age Factors↗
PubMed1996

Drugs during pregnancy: an issue of risk classification and information to prescribers.

The Swedish system for the classification of fetal risk of drugs was the first of its kind and was implemented in 1978. Drugs for use in pregnant women are classified in 4 general categories--A to D. The US Food and Drug Administration (FDA) introduced a system in 1979 also using the letters A to D, together with an X category. However, the definitions differ considerably between the FDA system and the Swedish system, resulting in a very different allocation of drugs to the respective categories. In the Swedish system, category A includes drugs that have been extensively used and/or for which there are reliable clinical data indicating no evidence of disturbance of the reproductive process. Category B includes drugs for which data from pregnant women are insufficient for making any solid estimation of human teratogenic risk, and classification is therefore based on animal data, with allocation to 3 subgroups. For products in category C, the pharmacological action of the drug may have undesirable effects on the human fetus or newborn infant. Finally, category D contains drugs for which human data indicate an increased incidence of malformations. The categorisation statement is always followed by a short explanatory text. In contrast to the FDA system, the Swedish system has been well accepted, as judged by an interview study including 934 physicians and pharmacists. We believe that much of the American dissatisfaction may be a consequence of shortcomings in the category definitions of the FDA system. The FDA system requires an unrealistically high quality of data, e.g. the availability of controlled studies in pregnant women that fail to demonstrate a risk to the fetus are needed for a drug to be assigned to category A. Consequently, the majority of drugs on the US market are allocated to category C, interpreted as 'risk cannot be ruled out'. The distribution of drugs into the various categories is thus very different between the Swedish and FDA systems. We think that the issue of this debate reflects a fundamental problem related to public health information: how should a large, compounded, changing and difficult to evaluate databank be organised before it is made available to professionals and secondarily to lay people?

Australia↗
PubMed1995

Safety of acid-suppressing drugs.

There is an extensive literature on the adverse effects of drugs that inhibit gastric acid secretion. This study presents a critical examination of interactions between antisecretory drugs and other compounds, the frequency of serious adverse effects relating to various body systems, the safety of antisecretory drugs in pregnancy, and longer-term safety data from postmarketing surveillance studies. While interactions with some other drugs, alcohol, and certain carcinogens are of potential concern, in practice clinically significant reactions appear to be rare if they occur at all. A small number of major side-effects have been documented, but they occur rarely, and postmarketing surveillance has not detected other longer-term sequelae. Safety of these drugs in pregnancy is not established, as data are so few. It is concluded that antisecretory agents, by comparison with most other classes of drugs, are remarkably well tolerated.

Female↗
PubMed1993

The pharmacokinetics and pharmacodynamics of metoprolol after conventional and controlled-release administration in combination with hydrochlorothiazide in healthy volunteers.

We have studied a controlled-release formulation containing metoprolol 100 mg and hydrochlorothiazide 12.5 mg. We compared the pharmacokinetics of both substances and the pharmacodynamics of metoprolol with those of a conventional combination tablet. The controlled-release formulation gave less variable plasma metoprolol concentrations, Cmax 138 nmol.l-1 and Cmin 74 nmol.l-1, whereas for the conventional formulation the mean Cmax of metoprolol was 629 nmol.l-1 and the Cmin 20 nmol.l-1. Despite lower relative systemic availability (68%) for metoprolol from the controlled-release formulation and a smaller AUC, metoprolol from the controlled-release formulation produced a greater total effect, calculated as the area under the curve of the effect on exercise heart rate vs. time (303 vs. 259%.h; P < 0.05). Hydrochlorothiazide was rapidly absorbed from both formulations and the plasma concentration profiles were almost superimposable. Controlled-release metoprolol with hydrochlorothiazide combines effective beta 1-adrenoceptor blockade for 24 h without affecting the pharmacokinetics of hydrochlorothiazide.

Adult↗
PubMed1993

Effect of once daily intravenous and oral omeprazole on 24-hour intragastric acidity in healthy subjects.

The effect of repeated once daily administration of 20 mg omeprazole orally and 10 mg and 40 mg intravenously on 24-h intragastric acidity was studied in nine healthy subjects. On day 1, 20 mg orally and 10 mg intravenously reduced integrated intragastric acidity by 18% and 15%, respectively (NS). On day 5 the reduction had increased to 60% and 53%, respectively (p < 0.05). The first dose of 40 mg intravenously produced a reduction of 71% (p < 0.05) with no further increase during continued administration. An increase in plasma omeprazole concentrations by 56% (p < 0.05) was seen during repeated dosing with 40 mg intravenously, while no significant change occurred with the two other doses. Thus once daily administration of 10 mg omeprazole intravenously produced an effect on 24-h intragastric acidity comparable to that of once daily administration of 20 mg omeprazole orally. However, for both these dosage regimens it took a few days before their maximal effect was obtained. Parenteral administration of 40 mg omeprazole produced, already on the first day of treatment, an effect similar to that seen after 5 days of oral administration of 20 mg omeprazole or intravenous administration of 10 mg and can therefore overcome this initial delay in drug action. The reduction of 24-h intragastric acidity seen in the present study appeared to be lower than that seen in a similar study in duodenal ulcer patients, a finding not explained by differences in age or pharmacokinetics.

Administration, Oral↗
PubMed1992

Adverse event monitoring in clinical trials of felodipine and omeprazole.

Although most clinical trials encompass aspects of safety, methods for assessing the safety of a drug by recording adverse events have been poorly studied. It has been suggested that adverse events rather than adverse drug reactions should be monitored, since a reliable determination of which events were caused by the drug and which were not is only possible after analysing data from a substantial number of clinical trials. In the present study adverse events were monitored to see the extent to which events recorded on the case record forms were reported as adverse events. Data from omeprazole and felodipine programmes were used, comprising altogether 143 clinical trials from eight different projects, and encompassing 12,069 patients in whom 11,812 events were recorded. The first project was started in 1982 and the last in 1988. Overall, 74% of recorded events were entered on a special adverse event form used in the trials, and 26% were not. Initially, about 35% of adverse events were not reported as such, as opposed to 13% towards the end of the study period. Serious adverse events were reported less frequently than non-serious events, but in the most recent project all serious adverse events were reported. Adverse events in women were reported more often than adverse events in men, and reporting was more complete for the middle-aged than for the oldest and the youngest persons. Certain types of adverse events were reported more completely than others. In conclusion, the transition from registering adverse reactions to registering adverse events has been a gradual one in spite of intensive educational efforts when the projects were started.(ABSTRACT TRUNCATED AT 250 WORDS)

Adverse Drug Reaction Reporting Systems↗
PubMed1992

Safety experience from long-term treatment with omeprazole.

Omeprazole was administered for up to 6 years in 859 patients for 'prevention of relapse in patients with poorly responsive peptic ulcer or reflux oesophagitis'. The pattern of adverse events reported during long-term treatment was similar to the adverse-event profile in short-term treatment with omeprazole (n = 2,818), ranitidine (n = 1,572) and cimetidine (n = 891). Omeprazole had essentially the same adverse-event profile as the two H2-receptor antagonists. The adverse-event profile for omeprazole during long-term treatment did not differ from that seen during short-term treatment with either omeprazole or the H2-receptor antagonists. The rate of occurrence of any specific adverse event decreased with time, and no previously unidentified adverse event occurred with long-term omeprazole therapy. There were no serious adverse events that were considered to be causally related to omeprazole therapy. Thus, omeprazole has been shown to be well tolerated in both short- and long-term treatment.

Adolescent↗
PubMed1992

Pharmacokinetic study of omeprazole in elderly healthy volunteers.

The pharmacokinetics of omeprazole and its metabolites were studied in 8 healthy elderly volunteers using [14C]omeprazole. In another 6 healthy elderly volunteers, the pharmacokinetics of omeprazole were studied using unlabelled drug. Each volunteer received single doses of omeprazole intravenously (20mg) and orally (40mg) as solutions in a randomized crossover design. The plasma concentrations and urinary excretion of omeprazole and metabolites were followed for 24 and 96h, respectively. The results indicate that the average metabolic capacity of omeprazole is decreased in the elderly compared with that found in earlier studies of healthy young individuals. This was reflected in an increase in bioavailability from 56 to 76%, a reduction in mean systemic clearance by approximately 50% (0.25 L/min) and a prolongation of the mean elimination half-life from 0.7 to 1.0h compared with the young. Despite these findings, the considerable overlap in these parameters between young and old volunteers, together with data from previous pharmacodynamic studies and the wide therapeutic range of omeprazole, indicate that dosage reductions are not needed in the elderly.

Administration, Oral↗
PubMed1991

Lack of effect of omeprazole treatment on steady-state plasma levels of metoprolol.

In a randomised double-blind crossover study, seven healthy males were concomitantly given metoprolol 100 mg o.d. as a controlled release formulation, and omeprazole 40 mg o.d. or placebo, for 8 days. Plasma levels of the R- and S-enantiomers of metoprolol were determined on the 8th day of each treatment. The subjects were also characterised by their metabolic capacity to hydroxylate debrisoquine. Concomitant omeprazole treatment had no significant influence on the steady-state plasma levels of the two enantiomers of metoprolol. All subjects were characterised by extensive debrisoquine hydroxylation, i.e. extensive metoprolol metabolism. As metoprolol is metabolised to a great extent by debrisoquine hydroxylase (IID6), it is concluded that concomitant omeprazole treatment will probably have a negligible influence on the metabolism of the relatively large number of drugs mainly metabolised by this isoenzyme of the cytochrome P450 family.

Adult↗
PubMed1991

Determinants of migration in the Nordic labor market.

"Migration flows in the integrated Nordic labor market are heavily dominated by Finnish migration to Sweden. Differences in migration behavior across the Nordic populations are identified. Elasticities of migration are obtained from a logistic human capital model estimated as seemingly unrelated regressions. Differences in migration behavior are shown to exist, but the elasticities are not systematically higher for the Finns as could be expected. The domination of Finnish migration to Sweden is instead explained by real wage differences and since these have narrowed, major migration flows should not be expected in the future, unless large differences in labor market performance arise."

Demography↗
PubMed1991

An interpretation of the effects of age on migration: Nordic migrants' choice of settlement in Sweden.

A model of the relationship between age and migration is developed and applied to data concerning migrants from other Scandinavian countries who settled in Sweden between 1968 and 1985. The author shows "how changes in Sweden's domestic economic conditions and distance determine the probability for settlement in any of its 24 provinces for migrants of different ages. The results show that in the integrated Nordic labor market, wages at destination do not explain differences in migrants' settlement behavior across ages. Instead they suggest that the major factors to explain the differences are the labor market situation for the different age groups and distance."

Age Factors↗
PubMed1990

Pharmacokinetics of pafenolol after i.v. and oral administration of three separate doses of different strength to man.

The pharmacokinetics of pafenolol were evaluated in 12 healthy subjects after administration of three single IV doses (5, 10, and 20 mg) and three oral single doses (25, 50, and 100 mg). The drug was discontinuously absorbed. A first peak was observed 0.5 to 1.5 h after dosing and a second higher maximum concentration was noted 3 to 5 h after the administration in the majority of the experiments. The mean systemic availability increased from 27 +/- 5 per cent for the oral 25 mg dose to 46 +/- 5 per cent for the 100 mg dose, i.e., an increase of about 70 per cent (p less than 0.05). The half-life of distribution varied between 5 and 6 min and the apparent volume of distribution (Vz) was about 1.11 kg-1. The distribution was linear in the IV dose range studied. Total body clearance was about 300 ml min-1. About 50 per cent of the systemically available dose was excreted unchanged via the kidneys. Total body clearance decreased by about 13 per cent (p less than 0.05) by increasing the dose from 5 to 20 mg IV possibly because of reduced renal elimination. Mean terminal t1/2 of the IV dose was approximately 3.5 h. The corresponding t1/2 of the oral dose was approximately 6 h indicating absorption rate-limited kinetics of the oral dose.

Absorption↗
PubMed1990

Pharmacokinetic and pharmacodynamic evaluation of metoprolol controlled release (CR/ZOK) 50 mg in young subjects.

In this steady state, cross-over study, the bioavailability and beta 1-blocking effects of metoprolol CR/ZOK 50 mg, conventional metoprolol 50 mg tablets and placebo were evaluated in 12 healthy male subjects (mean age 25 years) after once daily treatment in 5 days. The drugs were administered in a randomized order. The beta 1-blocking effect was defined as percent reduction from baseline in exercise heart rate. The plasma concentration-time profile following metoprolol CR/ZOK 50 mg administration was more even compared to conventional metoprolol tablets, with significantly lower Cmax (mean: 71 vs 221 nmol/L) and significantly higher Cmin (mean: 39 vs 6 nmol/L) for the CR/ZOK formulation. This difference in plasma concentrations was also well reflected by a significantly lower fluctuation index for metoprolol CR/ZOK 50 mg compared with the conventional 50 mg tablet (mean: 69 vs 529%). There was, however, no difference in systemic bioavailability between the two metoprolol formulations (90% confidence limits: 86-106%). The beta 1-blockade was also more even after metoprolol CR/ZOK 50 mg compared to conventional tablets with a significantly lower Emax (mean: 14 vs 19%) and higher Emin (mean: 9 vs 0%) for CR/ZOK. The total effect over a dosage interval, defined as area under the effect curve, was significantly higher for metoprolol CR/ZOK compared to conventional tablets (90% confidence limits: 123-213%). In conclusion, once daily administration of metoprolol CR/ZOK 50 mg to young healthy subjects resulted in smooth plasma concentration and produced a significant beta 1-blocking effect for 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗