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Biomedical subjects

P Lundborg

Publications and source records attributed to P Lundborg.

At least 55 records · Page 3Linked to original sources
PubMed1985

Absorption, distribution and elimination of felodipine in man.

The objectives of these investigations were to study the absorption and disposition characteristics of felodipine in young healthy male volunteers following acute administration of different intravenous and oral doses, and to study urinary metabolites of [14C]felodipine following oral administration. Felodipine is rapidly and extensively absorbed from the gastrointestinal tract but owing to presystemic elimination, probably primarily in the liver, only 15% on average is systemically available. The systemic availability is independent of the oral dose in the 5 to 40 mg dose interval. The major fraction of the felodipine dose is localised extravascularly with a volume of distribution of about 10 L/kg. Less than 1% is confined to the blood. Felodipine is extensively bound to plasma proteins (greater than 99%). The mean elimination half-life of felodipine is greater than 10 hours. The urinary metabolic pattern of felodipine, using high pressure liquid chromatography, reveals 3 major metabolites (carboxylic acids of oxidised felodipine) in human urine.

Adult↗
PubMed1985

Acute diuretic/natriuretic properties of felodipine in man.

The natriuretic/diuretic effect of felodipine was investigated in 2 studies. The first was performed as an open study using intravenous and oral felodipine in healthy male subjects. The second was a double-blind study where a high and a low dose of oral felodipine were given to hypertensive patients on long term treatment with beta-blockers; the different doses of felodipine were chosen to decrease and to have no effect on the blood pressure, respectively. In both studies an oral placebo solution was used as a reference. Felodipine caused a significant increase in natriuresis. Compared with placebo and corrected for total 24-hour excretion, the sodium output during the first 4 hours after drug administration was increased by 219 +/- 53% (mean +/- SEM) after intravenous administration in healthy subjects (p less than 0.01) and by 80 +/- 43% in the first 3 hours after the high dose in hypertensive patients (p less than 0.05). For the same period, the urine excretion was increased by 114 +/- 38% (p less than 0.05) in the healthy subjects and by 36 +/- 22% in the hypertensive patients (not significant). However, the 24-hour excretion of urine, Na+ and K+ was not significantly changed from placebo. A significantly lower blood pressure was recorded after the higher dose (0.10 mg/kg) when given to hypertensive patients, but no such effect was seen after the lower dose (0.01 mg/kg) or in healthy subjects. The changes in diastolic blood pressure seem to be negatively correlated with the diuretic but not with the natriuretic effect.

Adult↗
PubMed1984

Pharmacokinetics of metoprolol in healthy, elderly, non-smoking individuals after a single dose and two weeks of treatment.

The effect of long-term treatment on the absorption and disposition of metoprolol has been evaluated in 8 healthy, non-smoking, elderly individuals (mean age 74.5 years) and in a control group of 8 healthy, young individuals. Two trace doses of [3H]metoprolol were given i.v., first concomitantly with a single oral 50 mg dose of cold metoprolol, and second, with the morning dose after 2 weeks of treatment with 50 mg b.d. In the elderly, the mean AUC increased by about 45% (p less than 0.05) over the treatment period, while in the control group the mean AUC was 18% greater (p less than 0.05) on Day 14 than on Day 1. In the elderly, changes both in pre-systemic elimination and in total body clearance accounted for the elevation of the AUC, whereas reduced first-pass effect appeared to be the major cause of the increased steady-state plasma level in the control group. With the exception of the volume term, V beta, the pharmacokinetic parameters were not significantly different between the elderly and the young individuals. For this reason, almost identical steady-state plasma levels were attained in the two groups. The results suggest that age-related physiological changes may have some minor effects on the pharmacokinetics of metoprolol, and also that the changes do not lead to significantly altered plasma concentrations compared to those in young individuals.

Administration, Oral↗
PubMed1984

Central GABA mechanisms during postnatal development in the rat: neurochemical characteristics.

Various biochemical characteristics of the developing GABA system was studied in rats from 1 to 60 days of age. Endogenous GABA concentrations were high in the limbic system, midbrain, brain stem and spinal cord at birth. Until 7 days of postnatal age, GABA concentrations generally decreased, thereafter an increase was seen and at 60 days of age the GABA concentrations exceeded those found in the neonate except for the spinal cord regions. After GABA-T inhibition with AOAA, GABA concentrations increased in all brain regions, however considerably more marked in the 28 days old rats compared to the 4 days old animals. Turnover rate of GABA was estimated by investigating the rate of disappearance of GABA after GAD inhibition with 3-MPA. Calculated turnover time of whole brain GABA was 34.1 min in the 4 days old rats and 19.9 min in the 28 days old animals. The results from this investigation clearly indicate a caudal to rostral maturational gradient in the development of endogenous GABA concentrations as well as synthesis capacity. Furthermore, turnover rate of total whole brain GABA but probably not of GABA in the neuronal pool is retarded in the 4 days old rats compared to the adolescent animals.

3-Mercaptopropionic Acid↗
PubMed1984

The effect of acetylsalicylic acid in 3 different formulations on in vitro and in vivo platelet function tests. An experimental study on healthy male volunteers.

The template bleeding time (TBT), ADP-induced platelet aggregation, and serum production of TXB2 were measured in healthy young male subjects immediately before, and on days 1, 4 and 6 after the ingestion of 1 single dose of 500 mg acetylsalicylic acid (ASA) in 3 different formulations: Aspirin (Bayer), and the 2 enteric-coated formulations Reumyl (Hässle) and Premaspin (Lääke). The ingestion of Aspirin resulted in a significant prolongation of the TBT over a period of 6 d. However, after the ingestion of the same amount of ASA in the 2 enteric coated formulations, the TBT as measured on day 6 had become normalized. After the ingestion of Aspirin, there was no reappearance of the second wave of ADP-induced platelet aggregation during the study period; however, after the ingestion of the 2 enteric-coated formulations, secondary platelet aggregation occasionally returned on day 6. In response to the intake of each of the 3 ASA formulations, the serum TXB2 production as measured 24 h later was almost completely inhibited. In each of the 3 study groups, the TXB2 formation as measured on day 6 was still significantly impaired.

Adult↗
PubMed1984

Drug use during pregnancy and breast-feeding. A classification system for drug information.

Since 1978 the Swedish catalogue of registered pharmaceutical specialties (FASS) has carried a special section entitled "Pregnancy and breast-feeding" in each product presentation, intended to form an aid for the prescription of drugs to women during childbearing and lactation. After a brief review of transplacental transport and milk secretion, reproduction-toxicology studies in animals, and methods for clinical evaluation of drugs for use during pregnancy, the classification system is presented. On the basis of available data with regard to effects on early and late stages of pregnancy and labour, all the pharmaceutical specialties concerned are assigned to one of the following pregnancy categories: A, B 1, B 2, B 3, C or D. The letters refer to information based on findings in man, and the figures to information based on animal data. For drugs in categories B 3, C or D any harmful effects observed or likely to occur in man or animals are to be specified. The pregnancy categories are defined as follows: Category A. Drugs which may be assumed to have been used by a large number of pregnant women and women of child-bearing age, without any form of definite disturbance in the reproductive process having been noted so far, e.g. an increased incidence of malformations or other direct or indirect harmful effects on the fetus. Category B. Drugs which may be assumed to have been used by only a limited number of pregnant women and women of child-bearing age, without any form of definite disturbance in the reproduction process having been noted so far, e.g. an increased incidence of malformations or other direct or indirect harmful effects on the fetus. Category C. Drugs which by their pharmacological effects have caused, or must be suspected of causing disturbances in the reproduction process that may involve risk to the fetus without being directly teratogenic. Category D. Drugs which have caused an increased incidence of fetal malformations or other permanent damage in man or which on the basis of e.g. reproduction-toxicology studies must be suspected of doing so. This category comprises drugs with primary teratogenic effects. If the drug also has pharmacological effects that may directly or indirectly have a harmful effect on the fetus, this must also be stated. As experience of effects of drugs in Category B is limited, results of reproduction-toxicology studies in animals are indicated by allocation to one of three subgroups according to the following definitions: Category B 1.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Drug-Induced↗
PubMed1984

Disposition of the adrenergic blocker metoprolol in the late-pregnant woman, the amniotic fluid, the cord blood and the neonate.

Pharmacokinetic studies on the concentration of the beta 1-blocker metoprolol have been performed in maternal plasma, amniotic fluid, breast milk and the plasma of the newborn. The concentration of metoprolol in maternal plasma exceeded that in the amniotic fluid initially , but not later on. The quotient between the metoprolol concentration in the maternal venous blood and the mixed cord blood at the time of parturition is at about 1. In the maternal plasma the metoprolol concentration decreases rapidly after the latest dose, probably because of an increased clearance rate. Blood levels of metoprolol during the first postnatal hours increase almost fourfold and are generally followed by a decrease over the next 15 hours. Active metabolites of metoprolol (alfa-OH-metoprolol and 0-demethyl-metoprolol) are found in the urine of the newborn. The breast milk concentration of metoprolol is three times as high as in the maternal plasma but the suckling newborn will only show very low or unmeasurable plasma levels between consecutive breast feeding periods, in the majority of cases.

Amniotic Fluid↗
PubMed1984

Pharmacokinetics of lidocaine in healthy individuals pretreated with multiple doses of metoprolol.

The effect of pretreatment with multiple doses of 100 mg of metoprolol on the pharmacokinetics of lidocaine has been studied in six young healthy subjects. The lidocaine dose was 100 mg and the infusion time 12 minutes. Metoprolol had no effect on the levels or the time course of lidocaine in the plasma. The disposition characteristics of the antiarrhythmic agent were not significantly altered by metoprolol in these individuals. These results cannot be extrapolated to prolonged infusion of lidocaine in patients with myocardial infarction.

Adult↗
PubMed1983

Pharmacokinetics of metoprolol and its metabolite alpha-OH-metoprolol in healthy, non-smoking, elderly individuals.

The absorption and disposition of metoprolol have been evaluated in 10 healthy, non-smoking, elderly individuals (mean age 73.1 years) by simultaneous determination of [3H]-metoprolol and unlabelled metoprolol. The labelled drug was given as an intravenous tracer dose, immediately followed by oral metoprolol 25 mg. The experiment was preceded by administration of metoprolol 25 mg b.i.d. for 3 days. The volume of distribution, elimination half-life and total body clearance were almost the same as previously observed in healthy, young subjects. The mean systemic availability was about 39% in the elderly, which is lower than the mean of 55% observed in a control group of young volunteers who received 50 mg b.i.d. In the elderly, the mean plasma concentration of alpha-OH-metoprolol was about twice as high as that of the parent drug, whereas the opposite was true of the control group. The results indicate that age-related physiological changes have a negligible effect on the pharmacokinetics of metoprolol.

Adult↗
PubMed1983

Effect of gammahydroxybutyric acid on serotonin synthesis, concentration and metabolism in the developing rat brain.

5-HT synthesis, levels and degradation were investigated in the whole brain and regional brain areas in 4, 14, and 28 days old rats after administration of gammahydroxybutyric acid (GHBA). 5-HT synthesis was investigated by means of 5-HTP accumulation after decarboxylase inhibition by NSD 1015. 5-HTP accumulation increased in the 14 and 28 days old rats but decreased in the 4 days old animals 90 min after GHBA, 750 mg/kg. In the 28 days old rats a corresponding increase was also noted in the precursor amino acid tryptophan. Regional and whole brain 5-HT levels were not altered by GHBA treatment. Regional as well as whole brain levels of 5-HIAA increased in the 14 and 28 days old rats after GHBA administration. In conclusion, the present data indicate that GHBA increases the synthesis and degradation of 5-HT in adolescent rats. These effects of GHBA were not seen in the neonatal animals.

5-Hydroxytryptophan↗
PubMed1983

The effect of adrenergic blockade on potassium concentrations in different conditions.

A moderate increase in serum potassium concentrations has been observed in several controlled clinical trials with beta-blockers. This increase cannot be explained by the retention of potassium in the organism, and is probably caused by the redistribution of potassium from intracellular to extracellular compartments. beta-adrenergic mechanisms seem to be concerned in the extrarenal handling of the potassium-load in man, presumably by inducing an increased uptake of potassium in muscular cells and liver cells. These beta-adrenergic mechanisms are probably of the beta 2-type. In theory there are several conditions in which it is important to have a defence against hyperkalaemia from exogenous or endogenous sources for example, during heavy physical exercise, after a potassium-rich meal, or after traumatic tissue damage. Available data indicate that non-selective beta-blockade increases serum potassium concentrations during and after heavy exercise and during coronary bypass. The clinical implications of these findings are unknown.

Adrenergic beta-Antagonists↗
PubMed1983

The peripheral platelet count and ADP-induced platelet aggregation in response to metoprolol and propranolol as studied in young healthy male volunteers.

In previous studies, we have demonstrated that the oral administration of one single dose of metoprolol as well as of propranolol causes a significant increase in the venous platelet concentration. In the present study, we investigated the effect of metoprolol, administered twice daily over a period of 1 week, on the venous platelet count in a group of healthy volunteers. The results showed that the drug significantly raised the venous platelet concentration over the whole study period. Further, the effect of 1 week's metoprolol and propranolol medication on ADP-induced platelet aggregation was investigated in another group of healthy subjects; the results were compared to those obtained during 1 week of placebo medication. It was demonstrated that neither of the two beta-blocking drugs affected ADP-induced platelet aggregability; this was true on the first as well as on the last day of study.

Adenosine Diphosphate↗
PubMed1983

Disposition of the adrenergic blocker metoprolol in the late pregnant women, the amniotic fluid, the cord blood and the neonate.

Pharmacokinetic studies of the concentration of the beta 1-blocker metoprolol have been performed in maternal plasma, amniotic fluid, breast milk and the plasma of the newborn. The concentration of metoprolol in maternal plasma exceeds that in the amniotic fluid initially but not later on. The quotient between the metoprolol concentration in the venous maternal blood and the mixed cord blood at the time of delivery is at about 1. In the maternal plasma the metoprolol concentration will decline in a rapid way after the latest dose probably because of an increased clearance. Blood levels of metoprolol during the first postnatal hours will increase almost fourfold and are generally followed by a decrease over the next 15 hours. Active metabolites of metoprolol (alfa-OH-metoprolol and O-demethyl-metoprolol) are found in the urine of the newborn. The breast milk concentration of metoprolol is 3 times higher than in the maternal milk but the sucking newborn will only show very low or unmeasurable plasma levels between consecutive breast feeding periods in the majority of cases.

Adrenergic beta-Antagonists↗
PubMed1982

Effect of gammahydroxybutyric acid on catecholamine synthesis and utilization in the developing rat brain.

Gammahydroxybutyric acid (GHBA) was administered subcutaneously, 750 mg/kg, to 1, 4, 14 and 28 days old rats 30 or 90 min before sacrifice. Whole brain and regional brain levels of tyrosine, dopamine (DA) and noradrenaline (NA) were measured. In some experiments the tyrosine hydroxylase activity was studied by measuring the accumulation of dihydroxyphenylalanine (DOPA) after inhibition of aromatic L-aminoacid decarboxylase. GHBA induced an increase in tyrosine and DA levels at the various ages except at 1 day of postnatal age. The effect of GHBA on the accumulation of DOPA after inhibition of aromatic L-aminoacid decarboxylase varied with age. Thus, tyrosine hydroxylase activity seemed to be enhanced in the 4 days old rats after 90 min and after 30 min in the 28 days old rats. Ninety minutes after GHBA administration to the 28 days old animals, DOPA accumulation reached or was slightly below control levels. Brain NA levels were not affected by GHBA administration. Regional analysis of DA and NA after inhibition of tyrosine hydroxylase with alpha-methyltyrosine demonstrated a reduced disappearance of DA after GHBA in the striatum region already from 4 days of postnatal age. GHBA administration did not affect the nerve impulse release of NA in any of the brain regions studied. It may be concluded that GHBA acts inhibitory on brain DA neurons during early postnatal development.

Aging↗
PubMed1982

gamma-Aminobutyric acid concentrations in the cerebrospinal fluid of newborn infants.

gamma-Aminobutyric acid (GABA) concentrations in cerebrospinal fluid (CSF) were measured in 20 neonates with various gestational and postnatal ages. These concentrations varied between 9 and 45 nmol/ml which is approximately 20-100 times the concentrations found in adults. CSF GABA concentrations tended to decrease with advancing gestational age. No apparent alterations were noted with increasing postnatal age (until 6 weeks of age). Asphyxia but not neonatal sepsis was accompanied by an increase in CSF GABA concentrations compared to respective controls.

Asphyxia Neonatorum↗
PubMed1982

Monoamine synthesis and concentration in neonatal rat brain during hypercapnia and recovery.

One-day-old rats were exposed to a gas mixture of 15% CO2-21% O2-64% N2 for a 30-min period. Monoamine synthesis in whole brain was measured during, and at various intervals after, hypercapnia by estimating the accumulation of dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) after inhibition of aromatic L-amino-acid decarboxylase with NSD 1015. Endogenous concentrations of tyrosine, dopamine (DA), noradrenaline (NA), tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were measured at the same intervals. Exposure to CO2 induced an increased synthesis of catecholamines and 5-HT. Further, an increase in DA concentration was seen during hypercapnia, while NA and 5-HT were unchanged. After the CO2 exposure the increased in vivo synthesis rates of catecholamines and 5-HT were rapidly normalized, as was the endogenous DA concentration. A slight increase in 5-HT and 5-HIAA concentrations was seen immediately after CO2 exposure. These results indicate that in neonatal animals, hypercapnia induces changes in central monoamine neurons, primarily an increased synthesis. These alterations may be relevant to some physiological changes seen during CO2 exposure, such as the alteration in central respiratory performance.

5-Hydroxytryptophan↗