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Biomedical subjects

T B Vree

Publications and source records attributed to T B Vree.

At least 253 records · Page 14Linked to original sources
PubMed1983

The effect of the molecular structure of closely related N1-substituents of sulfonamides on the pathways of elimination in man. The acetylation-deacetylation equilibrium and renal clearance related to the structure of sulfadiazine, sulfamerazine and sulfadimidine.

Sulfadiazine, sulfamerazine, sulfadimidine and their corresponding N4-acetyl derivatives were administered to man. The percentages of acetylation and deacetylation, protein binding, half-lives of elimination and apparent and true renal clearance values were measured. Methyl substitution in the N1-pyrimidine ring favours acetylation by an additional N-acetyltransferase isoenzyme present in 'fast' acetylators only. Methyl substitution in the N1-pyrimidine ring favours renal clearance of the N4-acetylsulfonamide derivatives. The N1-substituent probably reinforces the binding of the N4-acetyl group to the active tubular transport mechanism. The renal clearance of these sulfonamides is not dependent on the structure of the N1-substituent.

Acetylation↗
PubMed1983

The effect of surgery on the renal excretion of beta 2-microglobulin.

Surgical trauma causes an increase in the renal excretion rate of beta 2-microglobulin whilst creatinine excretion is not influenced. The increase in the renal excretion rate of beta 2-microglobulin is probably the result of an increased release of beta 2-microglobulin by the cells which exceeds a maximum in the active tubular reabsorption of the compound by the proximal tubule cell. The renal excretion of beta 2-microglobulin is proportional to the relative clinical trauma score.

Beta-Globulins↗
PubMed1983

The acetylation-deacetylation equilibrium of sulfadimidine in ruminant calves.

Plasma disappearance curves of sulfadimidine (SDM) in calves show at high doses a pattern resembling that of capacity-limited elimination. The half-life of the first part of the elimination phase of SDM when administered at high doses ranged between 6.4 and 11.5 h, while that of the terminal end of the plasma concentration-time curves was similar to that obtained at a low level application, ranging between 2.5 and 6.0 h. The percentage of N4-acetylsulfadimidine (N4-SDM) in plasma was low, viz. 2.2 to 5.8% of the total sulfadimidine concentration measured. The acetylation-deacetylation equilibrium was established within 3 h p.i. The N4-SDM plasma concentration-time curves were parallel to those of SDM beyond 3 h p.i. At high doses (66-235 mg/kg) the percentage of N4-SDM was slightly higher than that found at the low dose level. A small proportion of N4-acetylsulfadimidine, injected as the parent compound, was deacetylated to SDM. The intrinsic elimination half-life of N4-SDM was 0.9 h. It may be concluded that ultra-trace concentrations of N4-SDM, left in edible tissues of ruminants at slaughter, have in case of negative sulfonamide-sensitive bioassays no significance for the public health.

Acetylation↗
PubMed1983

Effect of injection site on the bioavailability of an oxytetracycline formulation in ruminant calves.

The oxytetracycline (OTC) disposition was studied in a group of six calves following the administration of an oxytetracycline-10 per cent formulation (i) intravenously (i.v.), (ii) subcutaneously (s.c.) in the lateral neck, and intramuscularly (i.m.) in (iii) the lateral neck, (iv) the shoulder (M. triceps brachii), and (v) the buttock (M. semitendineus). The dose levels used for the intravenous route and other routes were respectively 17.0 +/- 2.3 and 18.3 +/- 1.25 mg OTC/kg. The peak OTC concentrations (Cmax) were achieved with the s.c. and i.m. routes between 4 and 8 hours after injection, the highest being found after application in the shoulder (Cmax:6.9 +/- 0.82 microgram/ml plasma). The Cmax for the s.c. and other i.m. routes in application was similar to each other, ranging from 5.0 to 5.5 micrograms/ml plasma. For different points in time after injection the partial bioavailability was calculated. At 52 h post injection (p.i.) maximal bioavailability was observed for the i.m. shoulder route, viz. 98.1 +/- 7.0 per cent of the administered dose, while at 76 h p.i. similar bioavailabilities were achieved for the i.m. neck and shoulder route, namely 93.3 +/- 8.9 and 99.4 +/- 4.2 per cent, respectively. The lowest bioavailability (83.1 +/- 13.4 per cent) was obtained following the i.m. buttock route at 76 p.i. An obvious irritating effect was observed after s.c. application in the neck an di.m. injection in the buttock, which had disappeared at 5 days p.i. It is assumed that the longer persistence of OTC in plasma resulting with the latter two routes of administration was due to this irritation effect.

Analysis of Variance↗
PubMed1983

Pharmacokinetics of the infusion of alfentanil in man.

The pharmacokinetics of alfentanil under the conditions of an empirically derived 1-h continuous infusion of 3 micrograms kg-1 min-1, with a bolus of 80 micrograms kg-1, both i.v., were determined in five patients. The distribution half-life (mean +/- SD) (7.4 +/- 3.1 min), elimination half-life (86.7 +/- 15.8 min), apparent volume of distribution, Varea (0.44 +/- 0.15 litre kg-1) and elimination clearance (3.33 +/- 0.75 ml kg-1 min-1) were similar to those previously reported for a single bolus of alfentanil. These values for apparent volume of distribution and clearance can be used to calculate correct bolus and infusion doses to maintain any desired steady state plasma concentration using standard formulae: for example, to maintain a steady state plasma concentration of 400 ng ml-1, a bolus dose of 176 micrograms kg-1 and an infusion of 1.3 micrograms kg-1 min1 would be required.

Adult↗
PubMed1983

Effect of age on the acetylation and deacetylation reactions of sulphadimidine and N4-acetylsulphadimidine in calves.

Following intravenous (i.v.) or intramuscular (i.m.) administration of sulphadimidine (SDM), the pharmacokinetics of SDM and N4-acetylsulphadimidine (N4-SDM) were studied in plasma of calves from the first day of life to the age of about 6 months. An obvious age dependency was observed for the elimination half-life (t1/2) of SDM: the first day of life the t1/2 ranged between 13.5 and 17 h, and decreased in approximately 3 weeks to 4-6 h and remained constant from this time. The metabolite N4-SDM, as a percentage of the total concentration of the sulphonamide measured in plasma of neonatal calves, ranged between 21.6 and 25.5% at the first day of life, declined in 3 weeks to approximately 12.8%, and at 5 till 9 weeks the final percentage was about 6.8%. Following administration of N4-SDM, the elimination half-life of N4-SDM was 3 h in an 8-day-old calf declined to 1.4-1.7 h in 4-week-old calves, and was 0.9 h in calves older than 11 weeks. The percentage of SDM (a metabolite of N4-SDM) in plasma increased with time after injection from 5.5 to 62.8% of the total sulphonamide plasma concentration. This value was age-related. The total body clearance of N4-SDM was three- to five-fold higher than that of SDM.

Acetylation↗
PubMed1983

Placental transfer and renal clearance of sulphamethoxazole and its metabolite N4-acetylsulphamethoxazole in a pregnant ewe.

Sulphamethoxazole and its metabolite, N4-acetylsulphamethoxazole, were shown to cross the placenta of a pregnant ewe. The plasma concentration of N4-acetylsulphamethoxazole increased in the foetus due to the limited elimination properties of the immature kidney. The amniotic fluid concentration of sulphamethoxazole and N4-acetylsulphamethoxazole were low, amounting to 2.0 and 0.46 micrograms/ml respectively. Protein binding of the sulphonamides was slightly higher in the foetus than in the ewe.

Animals↗
PubMed1983

Continuous monitoring of plasma antiepileptic drug levels.

Quantitative knowledge of the fate of antiepileptic drugs in individual patients is useful in the prevention, explanation, and correction of subtherapeutic and toxicity-causing regimens. Several variables, such as age and co-medication, require adaptation of the regimen. An interactive computer-assisted laboratory reporting service provides a data base with epidemiological options that helps in the daily management of patients and can supply information on pharmacokinetic parameters, local, regional, and national drug utilization, and disease frequency. Some treatment variables are quantitatively predictable, but many others require individual monitoring of clinical, behavioral, and laboratory observations by a multidisciplinary team of experts. Intensive monitoring by an epilepsy team in an institution for mentally retarded patients has allowed conclusions on the value of therapeutic substances, reduction of the number of simultaneously administered drugs, and seizure registration.

Anticonvulsants↗
PubMed1983

Some consequences of drug choice and dosage regimen for patients with impaired kidney function.

The object of this article is to discuss difficulties in extrapolating the performances of a drug for which the kinetic parameters are derived in healthy volunteers, to patients with severely impaired kidney function. The theoretical background of some actual or probable background is given, and a possible solution for these problems is offered, that is, choosing another drug from the same drug group. In patients without kidney function, metabolism is the only pathway of elimination. When the elimination of the metabolite formed occurs by means of renal excretion only, this metabolite accumulates in patients with impaired or absent kidney function. When a metabolic pathway of the parent drug is part of a metabolic equilibrium, the metabolic return reaction results in an "apparent parent compound," with a half-life identical to that of the accumulated metabolite. In this way, the concentration of the "apparent" parent compound increases and the half-life of the sum of parent and "apparent" parent drug will change. Examples of this drug behavior are given for sulfamethoxazole, sulfametrole, sulfamethizole, procainamide, and N4-acetylprocainamide.

Drug Synergism↗
PubMed1983

Clinical pharmacokinetics of drugs used in the treatment of status epilepticus.

Pharmacokinetics as the basis for dosage calculation for acute and subacute treatment of status epilepticus have been discussed. Bolus injection and intravenous infusion are the most common forms of drug administration in these cases. Rectal administration may be a good alternative in certain conditions. Intravenous diazepam and phenytoin are the first-line drugs against status epilepticus. Diazepam and sodium valproate have been reported to be effective by the rectal route. Depending on its pharmacokinetic parameters, each drug effect has a different onset, intensity, and time course.

Animals↗
PubMed1983

[Comparative study of thiopental and midazolam for induction of anesthesia].

In 40 female ASA class I-II patients, scheduled for laparoscopy, midazolam 0.2 mg kg-1 i.v. was compared with thiopentone 5 mg kg-1 i.v. for induction of anaesthesia after parenteral premedication. Loss of the eyelash reflex occurred significantly earlier (p less than 0.005) in the thiopentone group (23.3 s) than in the midazolam group (37.5 s). During orotracheal intubation a more stable cardiovascular course was found with midazolam than with thiopentone. Awakening was markedly slower with midazolam than with thiopentone. Anterograde amnesia of more than 60 minutes after induction of anaesthesia occurred in 50% of midazolam patients compared with 10% in the thiopentone group. No significant differences in side effects could be found. Midazolam 0.2 mg kg-1 was sufficient to induce anaesthesia reliably after premedication with droperidol and fentanyl shortly before induction.

Adult↗
PubMed1982

Simultaneous determination of dantrolene and its metabolites, 5-hydroxydantrolene and nitro-reduced acetylated dantrolene (F 490), in plasma and urine of man and dog by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method is described for the simultaneous determination of the skeletal muscle relaxant dantrolene and its metabolites, 5-hydroxydantrolene and nitro-reduced acetylated dantrolene (F-490), in plasma and urine of man and dog. The substances are detected spectrophotometrically at 375 nm. The detection limits are 0.02 mg/l. A preliminary extraction step into a choloroform-butanol mixture is required for the plasma samples. The method is suitable for pharmacokinetic studies of dantrolene.

Animals↗