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Biomedical subjects

A Sundwall

Publications and source records attributed to A Sundwall.

At least 37 records · Page 2Linked to original sources
PubMed1977

Disposition of three benzodiazepines after single oral administration in man.

Three benzodiazepines in equipotent doses: oxazepam 15 mg, dipotassium chlorazepate 10 mg and diazepam 5 mg, were administered in single, oral doses to seven healthy volunteers in a three-way cross-over study. The serum concentrations of oxazepam, N-desmethyldiazepam and diazepam were followed for 72 hours by gas chromatography and electron capture detection. The absorption of diazepam was most rapid and the mean time required to reach peak serum concentration was 45 minutes, followed by N-desmethyldiazepam 80 minutes and oxazepam 114 minutes. The serum concentration decay curves were biphasic with terminal mean half-lives of 48, 62 and 11 hours for diazepam, N-desmethyldiazepam and oxazepam, respectively. The mean and individual serum concentration time data were fitted to a two-compartment open model with first order absorption using a non linear least square program. The mean serum data fitted the model well. The same rank order was obtained with mean absorption half-lives as when comparing mean peak times while slightly shorter terminal half-lives were obtained in the curve fitting of mean serum data. Due to irregularities in the serum concentration time curves only five out of the 21 sets of individual data could satisfy the convergence criterion. The obtained parameters in the curve fitting were also accompanied with very large asymptotic standard deviations.

Administration, Oral↗
PubMed1977

First pass conjugation and enterohepatic recycling of oxazepam in dogs; intravenous tolerance of oxazepam in propylene glycol.

Oxazepam dissolved in propylene glycol was administered intravenously to dogs. There were no cardiac or general adverse effects. Hemolysis and thrombophlebitis were observed after rapid infusion (5.6 ml in 1 minute), and were shown to be due to the properties of the vehicle. Comparison of plasma concentration time curves after oral and intravenous administration indicated a bioavailability of 70 +/- 15 S.D. %. The decreased availability after oral dose was considered to be due to first pass elimination as the urinary recovery of metabolites was the same after the two routes of administration. This also indicates complete absorption. In a dog with a chronic biliary fistula 15 mg of oxazepam was given intravenously on two occasions. When normal bile flow into the gut was permitted the disposition of oxazepam was similar to that in normal dogs. When bile was withdrawn the elimination of oxazepam was more rapid with an increase of apparent plasma clearance. In this case 32% of the dose was excreted as conjugates in the bile within 3 hours after administration. In the normal dogs 2-20% of the dose given was recovered in the faeces as the parent compound and practically no conjugates were found. These findings indicate enteral hydrolysis of the conjugates, and a marked enterohepatic recycling or oxazepam.

Administration, Oral↗
PubMed1977

Comparative bioavailability of oral dosage forms of oxazepam--correlation with in vitro dissolution rate.

Four oxazepam tablet preparations and a suspension of micronized oxazepam in water were given to healthy, fasting volunteers in a comparative bioavailability study using a partial cross-over design. Urinary recovery (0-72 hours) was used as a measure of extent of absorption. Peak serum concentration was used as a measure of rate of absorption. The three dosage forms having the highest dissolution rate in vitro were absorbed to the same extent, while slower dissolving tablets were not as fully absorbed. Peak serum concentration correlated linearly with in vitro dissolution rate. Single oral doses of oxazepam tablets containing 10, 15 and 25 mg showed equal rates and extents of absorption and produced serum concentrations linearly correlated with dose.

Administration, Oral↗
PubMed1976

Biosynthesis of acetylcholine in different brain regions in vivo following alternative methods of sacrifice by microwave irradiation.

Endogenous acetylcholine and biotransformation of tritium-labelled choline (3H-CH) were studied in mouse brain regions following different methods of sacrifice, viz. dislocation of the spine (7 min until enzymes inactivated), whole body microwave irradiation (7 s) and irradiation of the head (0.25 s). The brain temperature was measured in different locations 10 to 60 s after irradiation. The slope of the temperature time curves indicated a brain temperature of about 85-90 degrees C at the termination of exposure to both types of irradiation. Acetylcholinesterase (AChE) and choline acetyltransferase (CAT) were practically completely inactivated when measured one to two min after sacrifice. For turnover studies, mice were killed 1, 5, 10 or 20 min after i.v. injection of 15 nmol of 3H-Ch. The brains were dissected into 6 regions, extracted and analysed. No significant difference (except in cortex) in the amount of endogenous ACh was found when whole body irradiation was used in comparison to dislocation of the spine. However, the amount of 3H-acetylcholine (3H-ACh) was much higher in the striatum, hippocampus and cortex, in particular. With the shorter inactivation time (head irradiation) endogenous ACh was markedly increased in the striatum, cortex, medulla, oblongata and midbrain. However, there was no further increase in the radioactive ACh. The difference regarding the post-mortem sensitivity of endogenous and radioactive ACh does not seem to have been due to methodological artifacts but rather suggests that they are handled differently by the brain tissue. Plots of the specific radioactivity (SA) of Ch and ACh vs. time indicated fairly distinct precursor-product relationship in the different regions, when the animals were sacrificed by irradiation of the head.

Acetylcholine↗
PubMed1975

Regional distribution of choline acetyltransferase in the human brain: changes in Huntington's chorea.

A stereotaxic method of tissue sampling has been developed permitting detailed studies of the distribution of choline acetyltransferase (CAT) in brains from controls and from patients suffering from Huntington's chorea. The characteristic pattern of CAT distribution within extra-pyramidal structures is described. In Huntington's chorea, CAT is unevenly reduced in several brain regions particularly in the rostromedial part of the caudate nucleus. The results indicate a preferential degeneration of neostriatal cholinergic neurones in Huntington's chorea.

Acetyltransferases↗
PubMed1972

Cerebrospinal fluid choline in extrapyramidal disorders.

Cerebrospinal fluid from patients with Parkinson's disease and Huntington's chorea has been investigated with regard to the concentration of choline. In Parkinson's disease the choline concentration of lumbar spinal fluid was not different from that of a control group, nor was it related to medication, duration of illness, or severity of symptoms. A comparison between choline in ventricular cerebrospinal fluid from patients with Parkinson's disease and with intention tremor showed no significant differences. Patients with Huntington's chorea had a lower concentration of choline in lumbar spinal fluid as compared with a control group. The results are discussed in relation to the possible sources of cerebrospinal fluid choline.

Acetylcholine↗