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Biomedical subjects

E Vinge

Publications and source records attributed to E Vinge.

50 records · Page 3Linked to original sources
PubMed1988

Partial characterization of endogenous digoxinlike substance in human urine.

Urinary samples were collected from individuals not taking cardiac glycosides. Aliquots of 30 ml were passed through preparative octadecylsilane-bonded phase columns and eluted in fractions by stepwise increasing concentrations of acetonitrile. Eluted fractions were analysed for their contents of endogenous digoxinlike substance (EDLS) by radioimmunoassay of digoxin and by a bioassay of cardiac glycosides, which measures the uptake of rubidium (86Rb) by erythrocytes as an index of Na+, K+-ATPase activity. In both assays, digoxinlike activity was found in several fractions, but the highest values were consistently measured in the fractions eluted with 40% acetonitrile. Greater amounts of EDLS were recovered from the urine of pregnant women than from the urine of men and nonpregnant women.

Acetonitriles↗
PubMed1986

Pharmacokinetics of nimodipine in patients with aneurysmal subarachnoid haemorrhage.

Patients with a ruptured supratentorial aneurysm undergoing early surgery after the subarachnoid haemorrhage were treated postoperatively with nimodipine to prevent delayed ischaemic dysfunction. It was given first as a continuous intravenous infusion 2 mg/h (mean dose 0.5 micrograms/kg/min) for at least 7 days, and then orally (45 mg X 6) for at least a further 7 days. During the i.v. infusion, the mean plasma concentration was 26.6 +/- 1.8 ng/ml. The plasma clearance ranged from 0.57 to 1.771/kg/h and was negatively correlated with the age of the patient. Immediately prior to successive oral doses, the mean plasma concentration was 13.2 ng/ml (range less than 3-38.8 ng/ml). The peak level was usually found after 1 h; it ranged from 7.0-96.0 ng/ml. Mean bioavailability was 15.9%. The nitropyridine metabolite was found in measurable concentrations only after oral treatment with nimodipine. In some cases, the concentration of metabolite exceeded that of the parent compound. The three patients investigated who developed delayed ischaemic dysfunction had plasma concentrations well within the range in patients who did not, so it seems unlikely that the therapeutic failure could be attributed to individual deviations in the pharmacokinetics of the drug.

Administration, Oral↗
PubMed1986

Pharmacokinetics of 14C-fenflumizole after intravenous administration to man.

The disposition of 14C-labelled fenflumizole was studied in five healthy subjects who received 0.1 mg/kg of fenflumizole as single intravenous doses. Radioactivity was measured in whole blood, plasma, urine and feces from prior to until 168 hours after dose administration. Chemical determinations of fenflumizole and its two demethylated derivatives in plasma were made by HPLC followed by fluorescence detection. Concentrations of fenflumizole calculated from radioactivity in plasma were consistently higher than from chemical determinations, suggesting the presence of metabolites. Radioactivity in blood cells decreased more slowly than in plasma. Plasma concentrations versus time could be described by a four-compartment model, with a terminal half-life of 119 hours (median). About 50% of the dose was excreted with the faeces, and about 4% was recovered in the urine. Unchanged fenflumizole in the urine accounted for 0.0001% of the total dose. Renal clearance of radioactive material decreased at low concentrations of radioactive compound in plasma, which may indicate changes in unbound fraction of drug and metabolites, or a saturable tubular reabsorption process. The slow elimination of fenflumizole is consistent with slow release from tissues and/or enterohepatic recycling.

Adult↗
PubMed1986

Compared effects of the two antiinflammatory drugs indoprofen and lonazolac on thromboxane generation and on platelet aggregation, related to plasma concentrations after single oral doses.

Single doses of indoprofen 100 mg and lonazolac-Ca 200 mg were given orally to eight healthy volunteers. Blood samples were taken prior to and at various times until 24 hours after the dose. Drug concentrations in plasma were analyzed by HPLC and thromboxane B2 (TXB2) in serum by radioimmunoassay. Platelet aggregation in plasma was induced by various concentrations of arachidonic acid and evaluated with respect to different phases in the aggregatory response. The drugs were rapidly absorbed and for both compounds the decline in plasma concentrations described two phases. Although concentrations of indoprofen were up to ten times higher than those of lonazolac, the two drugs were almost equally potent inhibitors of generation of TXB2, with IC50 for indoprofen of 1.4-1.5 X 10(-7) M and for lonazolac 2.1-3.0 X 10(-7) M. Their effects on the lag phase in platelet aggregation paralleled the inhibition of TXB2 formation. However, the rate and extent of aggregation were more inhibited by indoprofen than by lonazolac, and the discrepancy was greater than would be expected from concomitant values for TXB2 suppression. The rate of aggregation appeared to be the most sensitive variable, since the extent of aggregation followed an all-or-none pattern. The present results show that the concentrations reached after clinically used doses of antiinflammatory drugs may vary widely in relation to the concentrations needed for maximum inhibition of platelet cyclooxygenase. The results from aggregation tests may support the idea that non-steroid antiinflammatory drugs can differ in their mechanisms of action.

Adult↗
PubMed1986

Cerebral vasospasm and calcium channel blockade. Nimodipine treatment in patients with aneurysmal subarachnoid hemorrhage.

In patients with aneurysmal subarachnoid hemorrhage (SAH), delayed ischemic cerebral dysfunction (DID or symptomatic vasospasm) with subsequent fixed neurological dysfunction (FND) is a frequent and most feared complication induced by the hemorrhage. Aneurysm operation during the acute stage with intraoperative evacuation of bloodcontaminated cerebrospinal fluid (CSF) from the basal cisterns and subarachnoid spaces has reduced this complication. Nevertheless despite early operation, DID with FND occurs in 13-20% or more. In a series of 100 individuals with a ruptured supratentorial aneurysm, who were subjected to aneurysm operation in the acute stage and who subsequently received intravenous treatment with the calcium channel blocker nimodipine, the occurrence of DID with FND was reduced to 5%.

Brain Ischemia↗
PubMed1985

Arachidonic acid-induced platelet aggregation and prostanoid formation in whole blood in relation to plasma concentration of indomethacin.

A single oral dose of indomethacin 1 mg/kg was given to 6 male and 6 female volunteers. The formation of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in clotting whole blood was measured by radioimmunoassay, and platelet aggregation induced by arachidonic acid (AA) was measured with a plasma aggregometer. The results were related to the concomitant plasma concentration of indomethacin. The maximum plasma concentration ranged between 3.24 and 8.11 micrograms/ml and the elimination half-life between 4 and 11 h. Formation of the prostanoids was reversibly inhibited, with maximum suppression when the drug concentration in plasma exceeded 0.5-1.0 microgram/ml; the IC50 was approximately 0.1 microgram/ml. Platelet aggregation was also reversibly inhibited. The correlation between the formation of prostanoids and the different phases of the aggregatory response to exogenous AA is discussed.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Single intravenous and oral doses of fenflumizole: pharmacokinetics and effects on prostanoid formation.

Fenflumizole is a substituted triaryl-imidazole with anti-inflammatory activity. Its disposition in man was studied after single intravenous and oral doses to 8 healthy male volunteers. Formation of the prostanoids thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-k-PGF1 alpha) in clotting blood was studied concomitantly. The pharmacokinetics after intravenous doses (0.1 mg/kg) could be fitted to a three compartment model and the half-lives (t 1/2) corresponding to the three phases were 2 min., 1 hour and 15 hours, respectively. The volume of distribution was 386 l and the plasma clearance 0.5 l per min. Oral doses (0.5 mg/kg) were rapidly absorbed (t 1/2 = 0.2 hr) and the following elimination from plasma had two phases with half-lives of 1 hour and 14 hours. Bioavailability was 50% due to a pronounced first-pass effect. The two metabolites mono- and didemethylfenflumizole were detected after both oral and intravenous doses and their maximum plasma concentrations occurred after 1-2 hours irrespective of the administration route. A concentration dependent depression of prostanoid formation was seen, the IC50 for TXB2 and 6-k-PGF1 alpha being 19 and 53 ng/ml respectively.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Effects of fenflumizole on aggregation ex vivo of human platelets and formation of thromboxane B2 and 6-keto-prostaglandin-F1 alpha.

Fenflumizole (2-(2,4-difluorophenyl)-4,5-bis(4-methoxyphenyl)imidazole), a new non-steroidal anti-inflammatory drug, was given to healthy subjects in single oral doses of 0.1, 1 and 2 mg/kg. The effect of the drug was followed for up to 8 h by repeated tests of arachidonic acid-induced platelet aggregation and was related to its concomitant plasma concentration. Fenflumizole reversibly inhibited platelet aggregation and the degree of inhibition was found to be linearly correlated with the log plasma concentration. There was depression of the formation of thromboxane B2 and 6-keto-prostaglandin F1 alpha (the stable metabolites of thromboxane A2 and prostacyclin) in clotted whole blood measured by radioimmunoassay after fenflumizole 1 mg/kg. This effect was directly related to the concentration of the drug in plasma, the maximum effect being reached at fenflumizole concentrations greater than 200 ng/ml. EC50-values for inhibition of the formation of thromboxane B2 and 6-keto-prostaglandin F1 alpha were approximately 20 and 40 ng/ml, respectively. The results suggest that orally administered fenflumizole is a potent inhibitor of platelet aggregation and prostanoid formation.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

On the pharmacokinetics of fenflumizole, a novel antiinflammatory agent, after single oral administration to healthy subjects.

The disposition of fenflumizole, a recently developed imidazole derivative which inhibits prostanoid formation, was studied after single oral administration to eight healthy subjects. Fenflumizole was given in the doses 0.1, 1 and 2 mg/kg as an aqueous suspension. Plasma concentrations within the first 24 hrs were amenable to a two-compartment open model and showed a rapid absorption with a half-life of about 0.5 hr and peak concentrations in plasma after about 1 hr. The elimination phase became dominating after about 10 hrs with a half-life of 14-15 hrs. Peak plasma levels and areas under the concentration-time curves prior to onset of the elimination phase indicated a small reduction of the bioavailability with dose on comparison of the highest and the lowest dose (P less than 0.05) but for the whole observation period of 24 hrs no dose-dependent bioavailability was revealed. The mean transit time in plasma ranged from 21 to 22 hrs. Two metabolites (demethylation products) were detected in both plasma and urine. Their plasma concentrations amounted to only about 5% of those of the parent compound, and they were rapidly eliminated. The total urinary recovery of the intact fenflumizole and the two metabolites was less than 0.1% of the given doses. The renal clearance of fenflumizole was estimated to about 0.02 ml/hr.

Administration, Oral↗
PubMed1984

Effects on aggregation of human platelets of two xanthines and their interactions with adenosine.

Adenosine receptor antagonism has been suggested to be the cellular basis for many extrapulmonary actions of xanthine derivatives, such as theophylline. Enprofylline (3-propylxanthine) is a poor adenosine antagonist but is five times as potent as theophylline as a bronchodilator in man. Adenosine is a potent inhibitor of platelet aggregation, but also xanthines are considered to exert this action. In the present study, effects of theophylline and enprofylline on ADP-induced aggregation of human platelets were studied in vitro. Theophylline alone in concentrations exceeding 280 microM inhibited platelet aggregation concentration-dependently. Enprofylline alone mimicked this effect but was about five times more potent than theophylline. At the lowest concentrations used, corresponding to upper therapeutic levels, neither of the two xanthines affected platelet aggregation by ADP. The interactions between these low concentrations of the xanthines and adenosine were then evaluated. In the presence of theophylline 110 microM the inhibitory effect of adenosine 4 microM was attenuated, whereas the presence of enprofylline 21 microM enforced the inhibitory effect of adenosine. Thus, at low concentrations where neither theophylline nor enprofylline inhibits platelet aggregation theophylline antagonizes the antiaggregatory effect of adenosine, whereas enprofylline acts in synergy with this nucleoside.

Adenosine Diphosphate↗
PubMed1984

Outcome in 60 consecutive patients treated with early aneurysm operation and intravenous nimodipine.

Sixty consecutive patients with a ruptured supratentorial aneurysm underwent operation during the acute stage, 56 of them within 72 hours after the first bleed, one on the 4th day, and three on the 5th day. Six patients were classified preoperatively in Hunt and Hess neurological Grade I, 39 in Grade II, 11 in Grade III, and four in Grade IV or V. Nine patients had severe intracerebral hematomas, and one patient had a subdural hematoma. After the aneurysm was clipped, nimodipine was applied to the exposed arterial segments in a 2.5 X 10(-5)M solution for 10 minutes. Subsequently, all patients received a continuous intravenous nimodipine infusion (2 mg/hr) for 7 to 12 days, followed by oral treatment (270 mg/day). Forty-six patients (77%) made a good neurological recovery; the morbidity rate was 22%, and mortality rate 1.5%. Of the 45 patients in good condition (Grades I to II) preoperatively, 38 (84%) made a good neurological recovery. Two patients (3% of the total series) developed a typical picture of cerebral ischemic dysfunction of delayed onset with subsequent fixed neurological deficits. The results favor the opinion that early operative intervention is beneficial in patients in good condition rather than delaying surgery, and indicate that nimodipine provides an additional anti-ischemic effect. The appearance and severity of late angiographic vasospasm did not seem to be affected by nimodipine.

Adult↗
PubMed1983

Biological availability and pharmacokinetics of tinidazole after single and repeated doses.

Tinidazole was administered to healthy volunteers and serum concentrations were measured following single oral and intravenous doses and after repeated dosage at different dose levels. The elimination half-time was 12-13 h. Pharmacokinetics did not change with dose, route of administration or repeated dosage. The bioavailability of single oral doses ranged between 88 and 129% with a mean of 99%. Serum concentration curves tended to have double peaks or plateaus at about 4-6 h. 74% of the intravenous dose was eliminated from serum at 24 h, but only 19% was recovered in the urine, suggesting alternative ways of elimination. Excretion in the bile and a subsequent enterohepatic circulation may explain the variations in bioavailability and the shape of the serum concentration curves.

Adult↗
PubMedDate not supplied

Pharmacokinetic evaluation of a case of massive sotalol intoxication.

OBJECTIVE: To describe serum concentrations and clearance of sotalol after a massive overdose. CASE SUMMARY: A 37-year-old white man took 11.2 g of sotalol hydrochloride tablets in a suicide attempt. The first serum d,l-sotalol concentration 3 hours after taking the first tablet was 20.6 mg/L and the last measured concentration 59 hours later was 1.8 mg/L. Logarithmic transformation of the concentration data indicated two separate monoexponential phases in the elimination curve, with half-lives of 30.1 and 11.6 hours. DISCUSSION: The shorter serum half-life in the later phase is comparable with that in four previously reported sotalol intoxications and within the normal range. The elimination rate increased in a temporal manner with an increase in systolic blood pressure about 30 hours after the patient was admitted. Since the sotalol elimination rate depends principally on renal function, we believe the initially slow elimination is due to a temporary reduction of the renal function caused by the systolic hypotension. CONCLUSIONS: An initial phase of slow sotalol elimination may occur after severe overdoses. In our patient this was probably due to hypotension. Thus, blood pressure should be monitored carefully.

Adult↗