PubMed Health⌕ Search

Biomedical subjects

A Crema

Publications and source records attributed to A Crema.

At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Pharmacokinetics of oxiracetam following intravenous and oral administration in healthy volunteers.

The kinetics of oxiracetam after single intravenous and oral doses (2000 mg) were investigated in four healthy volunteers. Following intravenous administration, the decline in serum levels showed a prolonged, rapid phase followed by a delayed terminal phase. Mean residence times ranged from 3.9 to 6.5 h. Volumes of distribution ranged from 0.9 to 1.81 X kg-1, whereas clearance values ranged from 100 to 119 ml X h-1 X kg-1 More than 90% of the intravenous dose was recovered unchanged in the urine within 48 h. Oral administration resulted in peak levels within 1-2 h; thereafter, the decline in serum levels showed a pattern similar to that observed after the intravenous dose--almost 50% of the oral dose was excreted in the urine within 6 h. The absolute availability of oral oxiracetam was 75 +/- 7%.

Administration, Oral↗
PubMedDate not supplied

Stereoselective pharmacokinetics of moguisteine metabolites in healthy subjects.

We studied the pharmacokinetics of moguisteine, a racemic non-narcotic peripheral antitussive drug, in 12 healthy male subjects after a single oral administration of 200 mg. The unchanged drug was absent in plasma and urine of all subjects. Moguisteine was immediately and completely hydrolyzed to its main active metabolite, the free carboxylic acid M1. Therefore, we evaluated the kinetic profiles of M1, of its enantiomers R(+)-M1 and S(-)-M1, and of M1 sulfoxide optical isomers M2/I and M2/II by conventional and stereospecific HPLC. Maximum plasma concentrations for M1 (2.83 mg/l), M2/I (0.26 mg/l) and M2/II (0.40 mg/l), were respectively reached at 1.3, 1.6 and 1.5 h after moguisteine administration. Plasma concentrations declined after the peak with mean apparent terminal half-lives of 0.65 h (M1), 0.88 h (M2/I) and 0.84 h (M2/II). Most of the administered dose was recovered in urine within 6 h from moguisteine treatment. The systemic and renal clearance values indicated high renal extraction ratio for all moguisteine metabolites, and particularly for M1 sulfoxide optical isomers. Plasma concentration-time profiles and urinary excretion patterns for M1 enantiomers R(+)-M1 and S(-)-M1 were quite similar. Thus, for later moguisteine pharmacokinetic evaluations the investigation of the plasma concentration-time curve and the urinary excretion of the sole racemic M1 through non-stereospecific analytical methods may suffice in most cases.

Administration, Oral↗
PubMedDate not supplied

A double-blind, placebo-controlled clinical study on the effect of a standardized ginseng extract on psychomotor performance in healthy volunteers.

Various tests of psychomotor performance were carried out in a group of 16 healthy male volunteers given a standardized preparation of Korean ginseng (G 115; 100 mg twice a day for 12 weeks) and in a similar group given identical placebo capsules under double-blind conditions. A favourable effect of G 115 relative to baseline performance was observed in attention (cancellation test), processing (mental arithmetic, logical deduction), integrated sensory-motor function (choice reaction time) and auditory reaction time. However, end performance of the G 115 group was superior statistically to the placebo group only in mental arithmetic. No difference between G 115 and placebo was found in tests of pure motor function (tapping test), recognition (digit symbol substitution) and visual reaction time. No adverse effects were reported. It is concluded that G 115 may be superior to placebo in improving certain psychomotor functions in healthy subjects.

Adult↗
PubMedDate not supplied

Plasma protein binding of drugs in pregnancy.

The degree of binding to plasma proteins is an important determinant of drug disposition and response. Normal human pregnancy is associated with concentration of plasma proteins, free fatty acids and possibly other endogenous substances interfering with drug binding. The possibility of an associated change in plasma binding capacity therefore needs to be taken into consideration. Experimental studies conducted mostly in vitro have shown that the plasma protein binding of many (but not all) drugs is decreased during pregnancy, particularly during the last trimester. This phenomenon should be taken into account when interpreting serum concentrations of total (free + protein-bound) drug in clinical practice. Notable examples of drugs whose unbound fraction increases during pregnancy include diazepam, valproic acid, phenytoin, phenobarbitone, salicylic acid, pethidine, lignocaine, dexamethasone, sulphafurazole and propranolol. For many drugs, important differences have been demonstrated in the degree of protein binding between maternal and cord plasma. In some cases, this may provide an explanation for the finding of marked differences in total drug concentration between maternal and fetal plasma at the time of delivery.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Interpretation of drug levels in acute and chronic disease states.

Serum drug concentration monitoring can be an invaluable aid to patient management, particularly in certain pathological conditions when individualisation of dosage is particularly critical. To be clinically useful, however, drug levels must be interpreted in the context of all factors that could influence the correlation between the concentration of the drug in plasma and the intensity of action. Several such factors may be operating in acute and chronic disease states. For example, a number of pathological conditions are associated with marked changes in the fraction of free, pharmacologically active drug in plasma and this will result in disruption of the normal relationship between total serum drug level and effect, as seen for phenytoin in uraemia. An altered response to a given serum drug level in disease states may also be caused by changes in tissue distribution, by abnormal accumulation of pharmacologically active metabolites in plasma or by changes in end-organ responsiveness. The latter are best illustrated by the altered sensitivity to digoxin in patients with various conditions, including hypokalaemia and thyroid disease. In addition to the factors listed above, consideration should also be given to potential interactions with concomitantly used drugs and to the possibility of analytical errors, especially in view of the evidence that the performance of otherwise reliable drug assays may be grossly impaired in certain diseases (e.g. uraemia), due to abnormal plasma composition and/or accumulation of interfering metabolites. In view of these complexities, a correct interpretation of serum drug levels requires a good knowledge of clinical pharmacology and a close collaboration between physician and laboratory. In any case, serum drug concentrations, like other laboratory tests, are not a substitute for careful patient observation, and any decision about drug treatment should be primarily based upon evaluation of the clinical state and, whenever possible, direct measurement of drug effects.

Acute Disease↗
PubMedDate not supplied

Cholinergic contractions induced by GABA-A receptor activation in the guinea-pig ileum are inhibited by alpha-chymotrypsin and potentiated by diazepam.

The influence of alpha-chymotrypsin and diazepam on the phasic (mainly direct) and tonic (indirect, probably substance P-mediated) components of intestinal cholinergic contractions, induced by the GABA-A receptor agonist 3-aminopropane sulphonic acid (3-APS), was investigated in the guinea-pig ileum. alpha-Chymotrypsin, at a concentration (20 U/ml) not affecting submaximal Ach (0.1 microM) contractions, preferentially depressed the tonic component of the 3-APS (30 microM)-induced response. A brief exposure (10 or 60 sec) to diazepam (0.1 microM) potentiated both the phasic and the tonic contractions evoked by low (10, 30 microM) 3-APS concentrations. This potentiation was prevented by bicuculline (30 microM), hyoscine (1 microM) and flumazenil (1, 3 microM). These results provide further support for an involvement of a peptide neurotransmitter on GABA-A receptor-mediated cholinergic response in the ileum. The modulation of this response by diazepam is probably exerted through recognition sites resembling the "central type" benzodiazepine receptors.

Acetylcholine↗