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Biomedical subjects

F Andreasen

Publications and source records attributed to F Andreasen.

At least 91 records · Page 5Linked to original sources
PubMed1982

Pharmacokinetics and pharmacodynamics of thiopentone, A comparison between young and elderly patients.

The induction doses of thiopentone in eight elderly male patients (60--80 years) were significantly lower (p less than 0.01) than in eight young male patients (ranges 3.09--5.06 mg/kg body weight in the elderly and 4.88--8.11 mg/kg in the young). The sleep concentrations in venous as well as in arterial blood did not differ between the two groups. In the elderly the arterial concentrations were significantly higher than the venous (p less than 0.05). A three compartment open model was used to describe the disappearance of the drug from the venous blood. Significant increases were found in V3 (means 145.9 and 51.2 litres) and in T 1/2 beta (means 781 and 427 minutes) in the elderly. The redistribution rate constant, k1.2, was decreased in the elderly (p less than 0.05). By impedance cardiography 5 minutes after sleep mean percentages of the pre-induction value of cardiac output were 94.6% in the young and 87.0% in the elderly (p less than 0.05). In the young a correlation was found between cardiac output and induction dose (4 = 0.85, p less than 0.01).

Adult↗
PubMed1982

In vitro studies on the hydrolysis of frusemide in gastrointestinal juices.

To elucidate a possible explanation for a relatively low bioavailability, the hydrolysis of frusemide in gastrointestinal juices was studied in vitro at concentrations likely to be present in vivo. Between 1.0 and 4.4% of the frusemide molecules were hydrolyzed to 4-chloro-N-furfuryl-5-sulphamoyl-antranilic acid (CSA) after 1 h at 37 degrees C in gastric juices. The rate of hydrolysis was inversely connected to pH. No fall in frusemide concentration was observed and no CSA was found in duodenal juices after 4 h at 37 degrees C. In three buffer solutions with the same pH as three gastric juices frusemide was hydrolyzed to CSA at a lower rate than in the gastric juices (pH 1.2, P less than 0.15;pH 1.4, P less than 0.001; pH 1.6, P less than 0.001). The solubility of frusemide was significantly higher in gastric juice from two fasting subjects (83-104 mg l-1) than in buffer solutions with the same pH (52-58 mg 1-1). The solubility of frusemide was significantly increased (by 40-50%) in gastric juice obtained after pentagastrin stimulation compared with its solubility in the mixed gastric secretion obtained after fasting. The binding of frusemide to macromolecules was 28.0 +/- 9.7% in ventricular secretion after fasting while it was 1.4 +/- 2.6% in the fluid obtained after pentagastrin stimulation. It is concluded that a hydrolysis of frusemide in the stomach prior to absorption cannot explain the relatively low bioavailability of the drug observed after oral intake.

Biological Availability↗
PubMed1982

The individual variation in pharmacokinetics and pharmacodynamics of furosemide in young normal male subjects.

Following a 24 h control period in the ward 80 mg furosemide was injected intravenously to ten young healthy, male volunteers. The serum clearance of furosemide (Cls) was between 140 and 201 ml min-1 and on the average the renal clearance was 60% of Cls. During the initial 30 min period a maximum additional excretion rate of sodium of 3.3 mmol min-1 was reached at an excretion rate of 0.8 mg furosemide min-1. A marked initial drop in creatinine clearance (Clcr) was noted and Clcr(24 h) showed an average decrease of 12% after the drug administration. The serum concentration of potassium was decreased at 1 and 2 h after the injection and of sodium from 2 h and on. The concentration of albumin in serum increased by 3% (P less than 0.05) already after 5 min. After 2 h a maximum increase of 14% was reached. After 8 min diastolic blood pressure was increased by 13% (P less than 0.05), whereas systolic blood pressure reached a significant decrease gradually (7% after 3 h).

Adult↗
PubMed1982

Binding of sulfinpyrazone and its metabolites in human serum and in solutions of human serum albumin.

The binding of sulfinpyrazone its sulfone metabolite and its sulfide metabolite to serum protein was studied by equilibrium dialysis. At 20 micrograms/ml 99.1% of the parent compound was bound in serum, whereas 99.8% of the sulfide and 98.3% of the sulfone were bound at this concentration. The binding of the three compounds were studied in diluted serum and in solutions of human serum albumin (HSA). There was no evidence of binding to proteins other than albumin. The association constants to primary and secondary binding sites and the number of binding sites were calculated. For the sulfide a lower K1-value in serum (0.76 . 10(6)M-1) than in the HSA solution (1.8 . 10(6)M-1) indicated the possible presence of a competitively bound substance in serum. In undiluted serum no displacing effect of the sulfide on sulfinpyrazone binding was found when both compounds were present in a concentration of 20 micrograms/ml, but in a HSA solution a pronounced sulfide induced displacement of the sulfinpyrazone from its primary binding site was shown. Acetylation of HSA depressed the binding of sulfinpyrazone but in undiluted serum there was no other effect on sulfinpyrazone binding by the addition of acetylsalicylic acid than could be explained by the displacing effect of salicylic acid. At concentrations of 20 micrograms/ml of sulfinpyrazone and above 50 micrograms/ml of the displacing agent significant displacement was demonstrated with phenylbutazone, tolbutamide and salicylic acid.

Acetylation↗
PubMed1981

Correlation between propranolol in plasma and urine, renin-aldosterone system and blood pressure in essential hypertension.

Thirty patients with mild or moderate essential hypertension, and a fixed elevation of diastolic blood pressure, were randomly allocated to three groups and treated with propranolol 40 mg x 4 (Group 1), 80 mg x 4 (group 2) and 160 mg x 4 (Group 3). Blood pressure (BP), pulse rate (PR), plasma renin activity (PRA), plasma aldosterone concentration (PAC), total plasma propranolol (tPP), free plasma propranolol (fPP), and 24 h urinary propranolol excretion (UP) were determined at the end of four consecutive periods: (A) after four weeks without any treatment; (B) after two to three weeks during which the propranolol dose was gradually increased to the intended level; (C) after four weeks, and (D) after eight weeks of unchanged treatment. The maximum reduction in diastolic BP occurred after period B, and in systolic BP after Period C, for Groups 2 and 3, and for all groups together; for Group 1, however, the maximum diastolic BP reduction was first seen after period C. PR was reduced to the same level in all groups after period B. After period B, PRA an PAC fell in all groups, and remained reduced during C and D Group 1. After periods C and D, PRA and PAC in Groups 2 and 3 did not differ significantly from the levels after period A; tPP, fPP and UP were significantly correlated with the propranolol dose, and were lowest in Group 1 and highest in Group 3; UP was negatively correlated with systolic but not diastolic BP in Periods B, C and D. In contrast neither fPP nor tPP were correlated with systolic or diastolic BP. There was no significant correlation between PRA, PAC and changes in PRA or PAC on the one hand and tPP, fPP, UP, BP or changes in BP on the other. It was concluded that propranolol effectively reduced BP, but diastolic BP reduction was most rapidly obtained at 320 and 640 mg daily, that the activity of the renin -aldosterone system was initially suppressed in all group, but for unknown reasons it increased towards the control level after seven to eleven weeks of therapy with 320 and 640 mg/day, and that the reduction in systolic BP increased with higher doses of propranolol and with increasing urinary propranolol excretion.

Adult↗
PubMed1981

Influence of age and sex on the pharmacokinetics of thiopentone.

Thiopentone was given to eight women and eight men (60 - 70 yr). The disappearance of thiopentone from the venous blood was described by a three-compartment open model. The only significant difference between the sexes was a higher initial venous concentration in males. The dose (mg kg-1) for induction was 70% of the value (P less than 0.05) previously reported for a comparable group of younger men and women (20 - 40 yr). The volume of distribution V2 and V2 were larger in the elderly (P less than 0.05). The terminal half-lives were increased with advancing age (from 75% to 100% on average) (P less than or equal to 0.01). The clearance value was 50% greater in the older women than in a group of young women. For all groups a significant correlation between initial drug concentration and k12 supported th hypothesis that there distribution rate constant k12 is the predominant factor in the pharmacokinetic profile of a dose of thiopentone sufficient to obtund the eyelash reflex.

Adult↗
PubMed1981

Pharmacokinetics of thiopental in caesarian section.

Anaesthesia for planned caesarian section in nine women was induced with an i.v. thiopental injection. The injection was stopped when the ciliary reflex disappeared. 250-300 mg was given over 60-85 seconds. The concentration of thiopental in peripheral venous blood 20 s after the disappearance of the ciliary reflex varied from 4.3 to 33.7 micrograms/ml. The simultaneously obtained concentrations at delivery (11-25 min after the start of the induction) were 1.7-6.0 micrograms/ml in venous blood from the mothers and 1.3-5.5 micrograms/ml in cord vein blood. In two of the newborns, the Apgar scores were 8 and 9, in the other seven it was 10. The baby with Apgar score 8 was delivered after 25 min and had a concentration in cord vein blood of 3.5 micrograms/ml. The decline in the concentration of thiopental in the venous blood of the mothers was described by a three-compartment open model. The terminal half-life was relatively short, between 91 and 595 min. The blood levels of thiopental in the newborns were followed for 22-33 h. The terminal half-lives in the babies ranged from 616 to 2560 min.

Adult↗
PubMed1981

The use of HPLC to elucidate the metabolism and urinary excretion of furosemide and its metabolic products.

Three principles for the use of HPLC with spectrophotometric detection to determine the concentration of furosemide and of 4-chloro-5-sulfamoyl anthranilic acid (CSA) were studied. A reversed phase microbondapack C18 column was used for the separation of either unchanged furosemide (I), CSA (II) or the diazo product of CSA (III). The sensitivity of the methods for the determination of furosemide added to serum in vitro were for I 0.05, for II 0.020 and for III 0.01 microgram/ml. The methods I and II were used to study the excretion pattern in the urine of furosemide and CSA after intravenous injection of 80 mg to 10 normal subjects. An average of 48.1 +/- 9.8% (S.D.) of the furosemide was excreted during the first hour as unchanged furosemide. Simultaneously 1.9 +/- 0.8% of the dose was excreted as CSA. Only very low concentrations of CSA were found in serum and that metabolite apparently was excreted with a higher renal clearance than furosemide during the period 30-60 min. after the administration (30.3 +/- 145 ml/min. for CSA and 88 +/- 23 ml/min. for furosemide). During the 24 hour period following the administration 52.6 +/- 8.1 mg was excreted as unchanged furosemide and 11.4 +/- 5.2 mg as a glucuronidated product.

Adult↗
PubMed1980

Pharmacokinetics of thiopentone in a group of young women and a group of young men.

The average induction dose of thiopentone did not differ significantly when eight young women were compared with eight young men. In neither group did the dose increase with increased body weight. Clearance of thiopentone from venous blood was described by a three-compartment open model. The average volumes of V1 and V3 were greater in the females, but only the difference between the V3 values was significant (P < 0.05). Significant correlations (P < 0.01) were found between the initial drug concentrations and the k12 values. The slopes of the regression lines were 0.0029 for the women and 0.0038 for the men (0.1 < P < 0.2). It is suggested that the redistribution rate constant k12 is predominant in determining the sleep dose rather than the initial distribution volume V1.

Adult↗
PubMed1980

The binding of furosemide to serum proteins in elderly patients: displacing effect of phenprocoumon.

The percentual binding of furosemide (5 micrograms/ml) was slightly but significantly lower in serum from elderly patients than in serum from normal blood donors (96.5 +/- 0.7 versus 97.9 +/- 0.3). A significant positive correlation was demonstrated between protein binding and albumin concentration in serum. The reduced binding in the elderly could be explained by an observed decrease in the concentration of albumin in the elderly. The percentual binding did not change in samples obtained during the first hour after the intravenous administration of 40 mg furosemide. Of 4-chloro-5-sulfamoyl antranilic acid (CSA) and antranilic acid (A) about 60% were bound to serum proteins in vitro and none of these two compounds affected the protein binding of furosemide. The addition of phenprocoumon (PPC) caused significant decreases in the percentual binding of furosemide in serum (5 microgram/ml) at PPC values of 10 microgram/ml and more. The effect of PPC on the binding of furosemide was studied in vivo in 7 patients receiving 40 mg furosemide intravenously without and with the simultaneous intravenous administration of PPC (3 mg per 10 kg body weight). In good accordance with the in vitro experiments the modest average decrease in furosemide binding, caused by concentrations of PPC not exceeding 6.2 micrograms/ml, was not significant.

4-Hydroxycoumarins↗
PubMed1980

The binding of thiopental to serum proteins determined by ultrafiltration and equilibrium dialysis.

An ultrafiltration method is described by which it is possible to estimate the protein bound fraction of a drug at its original concentration in a serum sample. The determination is carried out at 37 degrees and pH 7.4. For thiopental no difference was found between the values of protein binding whether they were determined by the ultrafiltration method or by a less time consuming equilibrium dialysis against an equal volume of phosphate buffered isotonic sodium chloride solution. The equilibrium dialysis was used to measure the concentration of bound and unbound thiopental molecules and the binding parameters in a two class binding model were determined. No evidence was found for binding to other proteins than albumin. About one binding site belonging to the first class was found per 1000 albumin molecules whereas an average of about 5 secondary sites were found for each albumin molecule. The association constants for the primary class of binding sites were 3.4 X 10(6)M-1 for albumin and 13.3 X 10(6)M-1 for serum while the values for the secondary class were 2.2 and 1.2 X 10(3)M-1 for albumin and serum respectively. The estimates of association constants and number of binding sites were based on experiments with total thiopental concentrations ranging from 0.4 to 80 microgram/ml. In a phosphate buffered albumin solution with 2 g albumin per 100 ml, a pH increase from 5 to 8 caused an increase in protein binding from 36 to 76%. A Scatchard plot using data from experiments with increasing albumin concentrations resulted in a "plot" with positive slope. The use of a curve like this is discussed and it is concluded that the binding parameters for thiopental are influenced by the albumin concentration.

Dialysis↗
PubMed1980

The binding of aprindine to serum proteins with statistical considerations concerning the analysis of binding data.

The binding of the potent, basic antiarrhythmic agent aprindine to serum proteins was studied in solutions of human serum albumin (HSA, lyophilized, 98% pure, KABI) and in human sera. The percentual binding in serum (90.9-96.7%) was considerably higher than in HSA solutions. The binding in serum decreased from 95-97% to 91-93% as the aprindine concentration was raised from 4 to 15 micrograms/ml. The serum binding differed significantly in sera from three normal individuals. By plotting (Formula: see text), as a function of bound drug and performing statistical analysis of the curves a striking difference between the number of primary binding sites in serum and in HSA solution was found (N1 for the HSA solution was 0.0016 and for one serum it was 0.020 "per albumin molecule".) The association constants for the primary binding sites (K1) were 4.3 X 10(6)M-1 for serum and 2.1 X 10(6)M-1 for the HSA solution. Furthermore, the analysis indicated that considerably less than one secondary binding site was present for each albumin molecule in the HSA solution. Therefore, no binding of aprindine to albumin molecules has been demonstrated and it is concluded that the entire binding of aprindine in serum as well as in 98% HSA solutions may be due to the presence of acid protein molecules. In particular, low percentual binding in HSA solutions in spite of the high association constant can be explained by a very low concentration of the binding proteins. The addition of propranolol or phenprocoumon did not cause any displacement of aprindine. In the appendix statistical problems in the analysis of the binding curves are elucidated. The experimental variance and the statistical acceptability of the binding model are discussed.

Analysis of Variance↗
PubMed1979

Method of estimating the disposition of drugs in the Danish population by sampling reimbursed prescriptions.

A method by which for a small cost it is possible to obtain a quantitative expression for the utilization, disposition and cost of drugs in a Danish county of 500,000 inhabitants. The procedure makes it possible to follow reimbursed preparations, i. e., drugs considered essential for the treatment of diseases. The sale, in D kr., of reimbursed preparations to individuals comprises about 80% of the sale of preparations requiring prescription. And in turn the sale of the latter amounts to 80% of total drug sales to single subjects. The method is based on systematic utilization of all the information available on each prescription; concepts of 'Entry Parameters', 'Calculated Units' and 'Derived Units' was discussed; the 'units' concern frequency of prescription and age- and sex specific dose-frequencies (weight units or defined daily doses -- DDD's). The possibility of creating a base for calculation of the frequency of certain diseases and of side-effects of drugs is mentioned, and examples of the application of the method to certain categories of patients and to certain drugs are given. From limitations of the method it is concluded that it should be considered as a supplement to other complete methods for the study of drug consumption.

Age Factors↗