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Biomedical subjects

T B Vree

Publications and source records attributed to T B Vree.

At least 271 records · Page 15Linked to original sources

Org-NC45: a new steroidal non-depolarizing muscle relaxant.

Although pancuronium has fewest side effects compared to other currently used non-depolarizing muscle relaxants, it is still not the ideal relaxant. Its structural analogues have been studied to derive such an ideal relaxant. Org-NC45 meets the requirements for such a relaxant best and is therefore extensively studied. It is more potent than pancuronium, has a shorter onset and duration of action and is free from cardiovascular side effects. Histamine release could not be demonstrated. It can be easily reversed by neostigmine, pyridostigmine or 4-aminopyridine. Interaction with antibiotics and anaesthetic drugs is not different from that of pancuronium.

Humans↗

The defined daily dose per 100 bed-days as a unit of comparison and a parameter for studying antimicrobial drug use in a university hospital. A retrospective study of the effects of guidelines and audit on antimicrobial drug use.

Growing awareness of problems arising from over-use of antimicrobial agents has led to attempts to develop policies or guidelines for rational treatment. To follow the effects of guidelines, the percentage of patients receiving anti-microbial drug therapy, acquired from patient records, has been a frequently used parameter. In this paper the Defined Daily Dose (DDD) per 100 bed-days has been used instead. This parameter can be calculated by converting the number of units of antimicrobials, delivered to individual wards, to defined daily doses per bed-day. This parameter determines the probability of treating a patient with a particular drug, based on pooled data. The DDD per 100 bed-days has been used to follow changes in prescribing habits arising from the acceptance of and adherence to guidelines over a period of 5 years in a University Hospital.

Anti-Infective Agents↗

Pharmacodynamics of vecuronium and pancuronium in cats with and without ligated renal pedicles.

The pharmacodynamic behaviour upon continuous infusion and bolus administration of pancuronium and vecuronium was studied in cats with and without ligated renal pedicles. In all circumstances vecuronium had a shorter time course of action than pancuronium. Ligation of the renal pedicles, i.e. acute renal failure, did not significantly influence the time course of the respective neuromuscular blockades. It is suggested that uptake by aspecific binding sites of the compounds is the main determining factor in termination of the blockade. A difference between acute and chronic renal failure is expected to exist.

Acute Kidney Injury↗

The relationship between the renal clearance of creatinine and the apparent renal clearance of beta-2-microglobulin in patients with normal and impaired kidney function.

The renal clearances of creatinine and beta 2-microglobulin of patients with either normal or impaired kidney function were measured. The renal clearance of beta 2-microglobulin depends on the urinary pH and must be considered as an apparent renal clearance because after tubular reabsorption the compound is metabolized in the kidney. Impaired kidney function reduces the percentage of tubular reabsorption of beta 2-microglobulin.

Absorption↗

Treatment of a patient with impaired renal function with gentamicin-PMMA-beads.

150 gentamicin-PMMA-beads were implanted (+ 160 mg gentamicin i.v. preop.) in a woman aged 73 years and with severely impaired kidney function. Frequent determination of gentamicin plasma concentrations and renal functions were possible. The plasma concentration reached a plateau at approx. 3 micrograms/ml. No accumulation of gentamicin in plasma occurred.

Acute Kidney Injury↗

Kinetics of L-tryptophan in depressive patients: a possible correlation between the plasma concentrations of L-tryptophan and some psychiatric rating scales.

The plasma concentration and flux of L-tryptophan are abnormal in primary depressive patients, according to the literature. The plasma concentrations of L-tryptophan over a 6-h period after ingestion of 5 g L-tryptophan were investigated and did not differ significantly between depressive patients and controls during the absorption, distribution, and elimination phases. There was no correlation between the plasma concentrations with anxiety or depression scores, or with the excretion in urine of 17-hydroxycorticosteroids and xanthurenic acid during the 24 h after L-tryptophan. Treatment with either 125 mg pyridoxine (three times daily with meals) and L-tryptophan (3 g at 10 PM) or with maprotiline (100 mg at 10 PM) had no influence on the plasma concentrations of L-tryptophan after 2 or 4 weeks of treatment. This excludes L-tryptophan deficiency as a pathogenic factor of depression in the patients studied. No kinetic differences could be demonstrated in the depressive patients, making differences in body compartments or flux of L-tryptophan unlikely to be of pathogenic importance to depression.

Chromatography, High Pressure Liquid↗

Pharmacokinetics and mechanism of renal excretion of short acting sulphonamides and N4-acetylsulphonamide derivatives in man. Structural requirements of sulphonamides for active tubular secretion.

The pharmacokinetics of short acting sulphonamides and a series of N4-acetylsulphonamide derivatives has been investigated. Sulphonamides with a sulphur atom two atomic bond distances from the N1 atom are excreted by active tubular secretion, e.g. sulphamethizole, sulphaethidole and sulphathiasole. When the sulphur atom is replaced by an oxygen or nitrogen atom, active renal excretion no longer occurs. N4-acetylsulphonamides are excreted by active tubular secretion. The renal clearance values of the N4-acetylsulphonamides are not influenced by the substituent at the N1 position. Two groups of N4-acetylsulphonamides can be distinguished. One has a T1/2 of 4-6 h and a renal clearance value of 20-60 ml/min and the second has a T1/2 of 10-20 h and a renal clearance of less than 10 ml/min. N4-acetylsulphonamides are deacetylated to the extent of about 5%.

Adult↗

Renal excretion of sulphamethoxazole and its metabolite N4-acetylsulphamethoxazole in patients with impaired kidney function.

Plasma and urine concentrations of creatinine, sulphamethoxazole and its metabolite N4-acetylsulphamethoxazole were measured in patients with varying degrees of kidney impairment. The plasma elimination half-life of sulphamethoxazole is not influenced by the kidney function, while the half-life of the metabolite is fully dependent on the kidney function. The renal clearances of the metabolites and that of the parent compound under alkaline urine conditions are linearly related to the creatinine clearance. Kidney impairment affects only the renal clearance of the metabolite, whereas sulphamethoxazole is metabolized (acetylated) independently of kidney function.

Acetylation↗

Factors influencing the activity and fate of benzodiazepines in the body.

1 The clinical pharmacokinetics of the many benzodiazepines used to treat numerous and varied clinical conditions can be influenced by many factors. 2 Combinations of drugs efficacious in the central nervous system can change the onset, intensity and duration of effect as a result of pharmacological, physiological and pharmacokinetic actions. 3 Pharmacokinetic considerations indicate that short to medium long-acting benzodiazepines that depend on only glucuronidation for their major metabolic pathway are the drugs of choice in this category.

Anti-Anxiety Agents↗

Recent developments in the treatment of acute urinary tract infections.

A review of the recent literature on acute urinary tract infections reveals some unresolved problems and considerable discussion and reappraisal of the current diagnostic and therapeutic methods. In this review, the rationale for the diagnostic confirmation of the presence, extent and site of infection is presented. Recent developments in the treatment of acute urinary tract infections are discussed. Factors affecting the choice of drug and recent studies concerning the duration of therapy are detained. Studies concerning the treatment of urinary tract infections with trimethoprim alone are reviewed and results of the treatment of acute urinary tract infection with a single dose of trimethoprim at St Radboud Hospital are presented.

Acute Disease↗

Trimethoprim: clinical use and pharmacokinetics.

The recent marketing of trimethoprim (TMP) as a single drug has resulted in interest in the use of this drug to treat common infections. The history and antibacterial properties of TMP are reviewed. Indications for the clinical use of TMP are presented, and possible new uses for the drug are considered. The significance of adverse effects is discussed. The pharmacokinetic properties of TMP are reviewed with particular emphasis on the renal handling of the drug and its advantages over TMP/sulfonamide combinations in relation to renal function and toxicity.

Bacterial Infections↗

Circadian rhythm in plasma concentrations of gamma-hydroxybutyric acid in alcoholics.

Gamma-hydroxybutyric acid (GHB) was orally administered to six alcoholics at 09.00 and 23.00 h. The plasma concentrations of GHB show a clear circadian pattern, the area under the curve in the daytime experiments being 61% of that in the night experiments. The significance of alcohol dehydrogenase, the catabolic enzyme of GHB, for the difference is discussed. It is concluded that, although the activity of alcohol dehydrogenase in alcoholics is quantitatively disturbed, it remains subject to physiologic circadian activation.

Adult↗

Pharmacokinetics and pharmacodynamics of the muscle relaxant drug Org NC-45 and each of its hydroxy metabolites in dogs.

The pharmacodynamics and pharmacokinetics of Org NC-45 and each of its metabolites were studied in anaesthetized dogs. Only Org NC-45 and C3-deacetylated NC-45 produced neuromuscular blockade at the doses studied. The plasma half-lives varied from 3 to 15 min, and are about one third of that of the structurally-related compound pancuronium. Renal excretion was of the order 5-20% and the biliary excretion 7-20% 6 h after administration of each of the 4 compounds. The apparent volume of distribution after a 1 1/2 h infustion was of the same order as the extracellular fluid volume. It seems that no significant entero-hepatic recirculation occurs. Thus, long term continuous infusions of Org NC-45 may be safe.

Animals↗

Simultaneous determination and pharmacokinetics of midazolam and its hydroxymetabolites in plasma and urine of man and dog by means of high-performance liquid chromatography.

A HPLC (high performance liquid chromatography) method for the determination of 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a] [1,4]benzodiazepine (midazolam, Ro 21-3981, Dormicum) and its hydroxy metabolites has been developed. The half-life of elimination of midazolam and the glucuronides of the metabolites 1-hydroxymethyl-midazolam, 4-hydroxy-midazolam and 1-hydroxymethyl-4-hydroxy-midazolam are identical, 53 min in dogs and 90 min in man.

Aged↗