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Biomedical subjects

L Widlund

Publications and source records attributed to L Widlund.

12 recordsLinked to original sources
PubMed1988

Absorption of tranexamic acid as a prodrug in healthy volunteers.

The absorption of trans-4-(aminomethyl)cyclohexanecarboxylic acid (tranexamic acid, Cyklokapron) administered as the prodrug trans-4-(aminomethylcyclohexanecarboxylate hydrochloride (Kabi 2161) was investigated in 3 healthy volunteers. Kabi 2161 was given orally in doses of 1, 2, 3 and 3.5 mmol, respectively, and as a reference a clinical dose of 1.5 g tranexamic acid (9.6 mmol) was administered. At 3 mmol of Kabi 2161 the same maximum plasma concentration of tranexamic acid was obtained as with the reference drug but with Kabi 2161 it appeared earlier. The recovery of tranexamic acid in the urine 0-48 h after administration of Kabi 2161 was 84.7, 82.4, 89.4 and 97.5%, resp., of the increasing doses. For the tranexamic acid 37.0% could be recovered. A similar result was seen in the areas under the plasma concentration-time curves normalized for dose. With Kabi 2161, 13.1, 19.6, 14.4 and 14.3 mg.h/l.mmol were found compared to 8.0 mg.h/l.mmol with tranexamic acid. From these results it was concluded that Kabi 2161 markedly increased the bioavailability of tranexamic acid in man.

Adult↗
PubMed1987

Bioequivalence of Genotropin and Somatonorm.

The bioequivalence parameters, AUC, Cmax and Tmax were calculated from serum hGH concentration-time curves after subcutaneous injections of Genotropin (recombinant somatropin) and Somatonorm (somatrem) in a two-period crossover study in 11 healthy men aged 21-35 years. Cmax was 53.4 and 62.9 mIU/litre and Tmax was 5.3 and 4.0 hours for Genotropin and Somatonorm, respectively. Criteria for bioequivalence were fulfilled for AUC. The bioavailability of Genotropin given subcutaneously was determined from the data obtained in the study above, and after an intravenous injection of Genotropin in the same dose (0.1 IU/kg body weight). The measured bioavailability of 71% could be an overestimate due to interference by endogenous hGH.

Adult↗
PubMed1986

Low molecular weight heparin (KABI 2165, Fragmin): pharmacokinetics after intravenous and subcutaneous administration in human volunteers.

The pharmacokinetics of a low molecular weight heparin (LMWH) with a mean mw of 4000-6000 D (KABI 2165, Fragmin) was studied in 6 healthy volunteers after intravenous (iv) and subcutaneous (sc) administration of 120 U (anti FXa)/kg. The half-life in plasma of the anti FXa activity after iv injection was 119 +/- 17 min, the volume of distribution (Vd) 3.4 +/- 0.5 1 and the total clearence 20.5 +/- 2.5 ml/min. The maximal anti FXa activity determined 3 min after iv bolus injection amounted to 2.2 +/- 0.3 U (anti FXa)/ml with a corresponding increase of the APTT from 31 +/- 7 sec to 113 +/- 35 sec. The elimination of the anti FXa activity was a monoexponential first order process. After sc administration the plasma half-life of the anti FXa activity was longer than after iv injection, 228 +/- 40 min, corresponding to the absorption rate thus found to be the rate limiting step. After sc administration the peak was reached after 4 hours (0.6 +/- 0.1 U (anti FXa)/ml; APTT increase 5 sec). The bioavailability after sc injection was calculated to be 87 +/- 6%. As a consequence of the high bioavailability and long T1/2 of the anti FXa activity, Fragmin administered sc seems to induce adequate levels of heparin-like activity making this regimen worth further investigation as an alternative for the treatment of deep venous thrombosis.

Adult↗
PubMed1986

Tranexamic acid derivatives with enhanced absorption.

Derivatives of the antifibrinolytic drug tranexamic acid [trans-4-(aminomethyl)cyclohexanecarboxylic acid] containing one or two tranexamic acid moieties were synthesized. Most of the derivatives have good stability in acidic and neutral solutions but are easily hydrolyzed in plasma. By measuring the amount of tranexamic acid excreted in the urine after an oral dose, relative absorptions of a number of derivatives in the rat were estimated. Most of the derivatives showed greater absorption than tranexamic acid itself. 1-[(Ethoxycarbonyl)oxy]ethyl trans-4-(amino-methyl)cyclohexanecarboxylate hydrochloride was chosen for studies in man.

Animals↗
PubMed1979

Characterization of a membrane protein from cholinergic synaptic vesicles isolated from the electric organ of Torpedo marmorata.

Rabbits were immunized with cholinergic synaptic vesicles isolated from the electric organ of Torpedo marmorata. The resultant antiserum had one major antibody activity against an antigen called the Torpedo vesicle antigen. This antigen could not be demonstrated in muscle, liver or blood and is therefore, suggested to be nervous-tissue specific. The vesicle antigen was quantified in various parts of the nervous system and in subcellular fractions of the electric organ of Torpedo marmorata and was found to be highly enriched in synaptic vesicle membranes. The antigen bound to concanavalin A, thereby demonstrating the presence of a carbohydrate moiety. By means of charge-shift electrophoresis, amphiphilicity was demonstrated, indicating that the Torpedo vesicle antigen is an intrinsic membrane protein. The antigen was immunochemically unrelated to other brain specific proteins such as 14-3-2, S-100, the glial fibrillary acidic protein and synaptin. Furthermore, it was unrelated to two other membrane proteins, the nicotinic acetylcholine receptor and acetylcholinesterase, present in Torpedo electric organ. The antiserum against Torpedo synaptic vesicles did not react with preparations of rat brain synaptic vesicles or ox adrenal medullary chromaffin granules.

Acetylcholine↗
PubMed1976

Phospholipid turnover in Torpedo marmorata electric organ during discharge in vivo.

One electric organ of anaesthetized Torpedo marmorata was stimulated through electrodes placed on the electric lobe of the brain. Nerves to the other electric organ were cut to provide an unstimulated control. Glucose 6-[32P]phosphate was injected into each organ 16h before electrical stimulation. After stimulation for 10 min at 5 Hz, the organs were removed homogenized and centrifuged on a density gradient for the preparation of subcellular fractions. Stimulation increased the incorporation of 32P into phosphatidate, phosphatidylinositol and phosphatidylcholine. The increased phosphatidate labelling, but not that of the other two lipids, was seen in fractions rich in synaptic vesicles. Stimulation had no effect on ATP labelling. The phosphatidate content of most fractions fell slightly after stimulation, but amounts of other phospholipids were not affected.

Acetylcholine↗