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Biomedical subjects

T B Vree

Publications and source records attributed to T B Vree.

At least 217 records · Page 12Linked to original sources
PubMed1986

Drug utilization research in clinical practice.

This report describes the use of drug utilization studies in clinical practice, with special emphasis on future developments. It has been shown that pharmacy services affect prescribing patterns, have great potential for reducing health care costs, and are in a position to produce financial savings in drug therapy and drug use. However, it is essential to balance the drug utilization figures against the resulting outcome, and attention should be focused on the assessment of therapeutic results. To make therapeutic result assessment possible, end points need to be defined. Several examples of such end points are given and include incidence of nosocomial infections and postoperative wound infections. New parameters have been established to assess the severity of the illness and to follow the effect of drugs on the disease process in the form of an Index of Disease Activity (IDA). IDAs have been prepared for Crohn's disease, rheumatoid arthritis, and ankylosing spondylitis. It then becomes possible to link drug utilization data with a drug's influence on a disease, making drug utilization research a recognized discipline within the medical field.

Anti-Infective Agents↗
PubMed1986

Gentamicin-PMMA beads. Pharmacokinetic and nephrotoxicological study.

Five patients treated with gentamicin-polymethylmethacrylate (PMMA) beads were monitored during the treatment of nine to 14 days. Kinetic data of the gentamicin delivery were gathered constantly by multiple samples of blood and urine. The treatment with 48-360 beads caused a gentamicin serum concentration of 0.03-0.4 micrograms/ml and a renal excretion rate of 3-40 micrograms/min. The total amount of gentamicin excreted after the whole treatment was 20%-70%, with an in vivo half-life of 5.7-10 days. The gentamicin appeared to be released constantly during the entire treatment (nine to 14 days); the beads are kinetically slow release carriers. Despite precise measurement of tubular and glomerular renal function, no nephrotoxicity could be demonstrated. This local antibiotic gentamicin therapy may use the blood bone barrier effectively as a protection of the body against a very high local gentamicin concentration.

Adult↗
PubMed1986

Effect of tick-borne fever on the disposition of sulphadimidine and its metabolites in plasma of goats.

The effect of tick-borne fever (TBF) on the plasma disposition of sulphadimidine (SDM) and its metabolites in goats was studied. In uninfected goats, SDM was extensively metabolised mainly by hydroxylation, glucuronidation and to a minor extent by acetylation. In TBF infected goats the hydroxylation of SDM into 6-methylhydroxysulphadimidine (SCH2OH) as well as into 5-hydroxysulphadimidine (SOH) was markedly reduced (-57.6 and -63.6 per cent, respectively). An unidentified metabolite (metabolite X) was detected, which was largely glucuronidated in the uninfected goats. In the TBF infected goats the glucuronide derivatives of the X metabolite and of SOH were barely detectable. In TBF infected goats the plasma concentration of the N4-acetylated metabolite (N4-SDM) was decreased to a lesser extent (-22.1 per cent) than the hydroxy metabolites. Due to the diminished metabolism the elimination half-life of SDM was increased 1.8 times and the total sulphonamide body clearance was diminished compared with findings in the control experiments.

Animals↗
PubMed1986

Dantrolene plasma and urine concentrations after oral pretreatment for malignant hyperthermia: report of a case.

Dantrolene plasma concentrations and renal clearance calculations in a patient undergoing major surgery are reported. The family history was positive for malignant hyperthermia. Following oral pretreatment the plasma concentrations in this patient were not noticeably different from values obtained in a study in awake volunteers and which were thought to be effective. This is the first report of dantrolene measurements made during anaesthesia and in the post-operative period.

Administration, Oral↗
PubMed1986

Convulsive effects and pharmacokinetics of laudanosine in the rat.

Laudanosine, which is a degradation product of atracurium, is a convulsant drug in the rat. Laudanosine plasma concentrations were measured by high performance liquid chromatography after administration of both laudanosine and atracurium; protein binding and renal excretion of laudanosine were also determined. A continuous laudanosine infusion of 25 mg kg-1h-1, or less, did not cause convulsions. Eight times ED90 for twitch depression of atracurium gave rise to a laudanosine plasma concentration of less than 8 micrograms ml-1. The convulsive plasma-concentration level for laudanosine was over 17 micrograms ml-1 in the rat. The protein binding of laudanosine was 80%. The kidney excreted 15-20% laudanosine. We conclude that convulsive levels of laudanosine will be very unlikely in any species provided that normal atracurium doses are used no matter how long the procedure.

Animals↗
PubMed1986

Chemotherapy and pharmacokinetics of some antimicrobial agents in healthy dwarf goats and those infected with Ehrlichia phagocytophila (tick-borne fever).

The therapeutic efficacy and pharmacokinetics of oxytetracycline (10 mg kg-1), ampicillin (20 mg kg-1) and a combination (TSS) of trimethoprim (20 mg kg-1), sulphadimidine (50 mg kg-1) and sulphamethylphenazole (50 mg kg-1) were investigated in normal dwarf goats and in those infected with Ehrlichia phagocytophila. Goats given oxytetracycline or TSS intravenously showed improvement, whereas ampicillin was ineffective. The infected goats had significantly prolonged elimination half-life values for sulphadimidine and oxytetracycline. The disposition kinetics of ampicillin and sulphamethylphenazole showed no marked differences between the healthy and infected animals. The tick-borne fever model used in the present study can be of value in testing the therapeutic efficacy and pharmacokinetics of chemotherapeutic agents in rickettsial infections.

Animals↗
PubMed1986

Age and dosage dependency in the plasma disposition and the renal clearance of sulfamethazine and its N4-acetyl and hydroxy metabolites in calves and cows.

Plasma disposition, protein binding, urinary recovery, and renal clearance of sulfamethazine (SMZ), its N4-acetylsulfamethazine (N4-SMZ), and its 2 hydroxy metabolites--6-hydroxymethylsulfamethazine (SCH2OH) and 5-hydroxysulfamethazine (SOL)--and the glucuronide of the latter were studied in 7 cows and 7 calves to determine the relationship between these values and the age of the animal and dosage applied. A capacity-limited hydroxylation of SMZ into SCH2OH was observed in cows and calves given dosages of 100 to 200 mg/kg. A biphasic SMZ elimination curve and steady state in SCH2OH plasma concentration (6 to 15 micrograms/ml) were observed. The N4-SMZ plasma concentration-time curve was parallel to that of SMZ at the dosages and in all animals. The total body clearance and the cumulative urinary recovery (expressed as percentage of the dose) for SMZ and its metabolites depended on drug dosage and age of the animals. At dosages of SMZ less than 25 mg/kg, the main metabolite in the urine of calves and cows was SCH2OH (23% to 55.2%), whereas in calves given a larger dosage (100 mg/kg), the N4-SMZ and SOH percentages increased. The plasma protein binding of SMZ and its metabolites depended on the SMZ plasma concentration. Hydroxylation lowered the protein binding (from 75-80%) to 50%. The renal clearance of SMZ was dependent on urine flow in all animals. The renal clearance of the SCH2OH metabolite was 2 to 3 times greater than the creatinine clearance value; thus, this compound was excreted by glomerular filtration and partly by tubular secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1985

Comparison of linear and tapered intravenous infusion of methotrexate in oncochemotherapy. A theoretical approach.

In oncochemotherapy with methotrexate (MTX) a peripheral concentration greater than 0.45 mg/l and a plasma concentration less than 45 mg/l must be maintained for 20 h. The time periods required to reach and maintain steady-state concentrations after tapered and linear intravenous infusion were compared. Pharmacokinetic analyses according to a two-compartment model were used to calculate dosage regimens and concentration profiles by means of the Bayesian General Modelling Program (BM) and NONLIN. When the dosage regimen is based on a steady-state concentration in the peripheral compartment (which is the target compartment for MTX) tapered infusion reaches this concentration 40% faster and maintains it 12.5% longer, but no difference is found if the dosage regimen is based on a steady-state concentration in the central compartment. In theory the two-step 24-hour tapered infusion can be replaced by a bolus injection plus linear infusion in the ratio 1:2 of the total dose. These dosage regimens are to be preferred over linear infusion.

Humans↗
PubMed1985

High-performance liquid chromatographic analysis of baclofen in plasma and urine of man after precolumn extraction and derivatization with o-phthaldialdehyde.

A reversed-phase high-performance liquid chromatographic method for the determination of the skeletal muscle relaxant baclofen in human plasma and urine is described. Cation-exchange extraction, precolumn derivatization with o-phthaldialdehyde, and on-column concentration precede fluorimetric detection (excitation at 340 nm, emission at 460 nm). The precision of the assay was always better than 6%. Recoveries of standards added to plasma and urine were 92% and 93%, respectively. With a sample size of 0.5 ml, a detection limit of a few nanograms, and the possibility of analysing up to four samples per hour, this method is suitable for pharmacokinetic studies. An example is presented.

Adult↗
PubMed1985

In vitro antimicrobial activity of hydroxy and N4-acetyl sulphonamide metabolites.

Hydroxylated metabolites of sulphadimidine, sulphamerazine, sulphatroxazole, sulphamethoxazole, and sulphadiazine exhibited antimicrobial activity against Escherichia coli 28 PR 271 test strain ranging from 2.5 to 39.5 per cent of that of the parent drug. Trimethoprim addition potentiated the antimicrobial activity of these metabolites. N4-acetyl sulphonamide metabolites possessed no antimicrobial activity, nor did trimethoprim potentiated them.

Acetylation↗
PubMed1985

Dose dependent disposition of sulphadimidine and of its N4-acetyl and hydroxy metabolites in plasma and milk of dairy cows.

The disposition of sulphadimidine (SDM) and of its N4-acetyl (N4-SDM) and two hydroxy metabolites, 6-hydroxymethyl-(SCH2OH) and 5-hydroxyasulphadimidine (SOH), was studied in plasma and milk of dairy cows following intramuscular or intravenous administration of sulphadimididine-33.3% at doses of 10, 45, 50, and 100 mg/kg. The main metabolite in plasma as well as in milk was SCH2OH. The metabolite percentages, the final plasma elimination half-lives, and the time of peak SDM concentrations in milk are presented for different dosages. The concentrations of SDM and its metabolites in milk ran parallel to those in plasma beyond 4 hours p.i. The metabolite concentrations in plasma and milk were lower than those of the parent SDM. Sulphate and glucuronide metabolites could not be detected in milk. At high doses (45 mg/kg or more) and SDM plasma concentrations exceeding 20 micrograms/ml, a capacity limited metabolism of SDM to SCH2OH was noticed, viz. a steady state concentration of SCH2OH and a biphasic elimination pattern for SDM and SCH2OH in plasma and milk. The mean ultrafiltrate ratios of the milk to plasma concentrations with respect to SDM, SCH2OH, SOH, and N4-SDM were: 0.69, 0.22, 020, and 0.63, respectively. The total amount of SDM and its metabolites recovered from the milk after milking twice daily over the whole experimental time was less than 2% of the applied dose. A bioassay method allowed of detecting qualitatively SDM concentrations exceeding 0.2 micrograms/ml in plasma or milk. Withholding times for edible tissues and milk are suggested.

Animals↗
PubMed1985

Pharmacokinetics and renal clearance of oxytetracycline after intravenous and intramuscular administration to dairy cows.

Following intravenous administration of an oxytetracycline-HC1 and an oxytetracycline-dihydrate formulation to dairy cows, no statistical difference could be found between the pharmacokinetic parameters, derived from the three-compartment model, of these preparations. Urinary recovery was continued for a period of 72 h following intravenous or intramuscular OTC administration. The recovery of OTC in the urine in the 72-h period was in the range of 73% to 96% of the available dose administered. The renal OTC clearance, the renal creatinine clearance, the urinary flow, and the interrelationships of these were determined on the basis of urine and plasma data. The mean OTC renal clearance ranged from 482 to 1050 ml/min and the creatinine clearance from 651 to 1304 ml/min. The OTC and creatinine clearances were significantly correlated to the urine flow up to 30 ml/min. The total body clearance and renal clearance values were of the same order of magnitude, and along with the urine recovery data they provided evidence of predominantly renal route of OTC elimination in dairy cows. The renal OTC elimination is the net result of mainly glomerular filtration, partly tubular secretion, minus reabsorption in the urogenital tract.

Animals↗
PubMed1985

Comparative pharmacokinetics and bioavailability of eight parenteral oxytetracycline-10% formulations in dairy cows.

In plasma and milk the oxytetracycline (OTC) concentrations were determined following a single intramuscular administration of eight 10%-formulations to dairy cows at a dose of approximately 5 mg/kg. Two of these formulations were injected intravenously to obtain reference values of the drug's pharmacokinetic parameters. The eight formulations were compared and evaluated pharmacokinetically with respect to absorption rate, peak plasma and milk OTC concentrations, biological half-life, and relative bioavailability. The mean maximum plasma OTC concentrations, ranging from 2.0 to 4.1 micrograms/ml, were achieved between 4 and 12 hours post injection, depending on the formulation involved. The mean maximum milk OTC concentrations, in the range between 0.92 and 1.43 micrograms/ml, were achieved 12 to 24 h p.i. The OTC milk concentration-time profile ran parallel to the OTC plasma concentration-time profile. After intravenous administration the time for the appearance of OTC in milk was shorter (1-2 hours p.i.), the peak milk OTC concentration was higher (1.7-1.9 micrograms/ml) and achieved earlier (6-8 h p.i.), and the OTC persistence in milk shorter than after i.m. administration. Formulations exhibiting the lowest clinically noticeable irritation showed the most favourable pharmacokinetic characteristics: rapid absorption with the highest peak plasma OTC concentrations and good bioavailability. The plasma and milk protein binding for OTC was respectively 71.7 +/- 7.4% and 84.8 +/- 5.45%. Withdrawal times for milk and edible tissues are presented on the basis of preset tolerance or detection limits.

Animals↗
PubMed1985

Interaction of midazolam with two non-depolarizing neuromuscular blocking drugs in the rat in vivo sciatic nerve-tibialis anterior muscle preparation.

Studies of the possible interactions between the water-soluble benzodiazepine, midazolam, and two non-depolarizing neuromuscular blocking drugs, vecuronium and tubocurarine, were performed in the rat in vivo sciatic nerve-tibialis anterior muscle preparation. Midazolam 0.5 and 5 mg kg-1 caused 17% and 34% depression of the twitch height, respectively, once a steady-state blockade of the twitch height had been induced by vecuronium. The potentiation of the tubocurarine steady state blockade by midazolam 5 mg kg-1 was quantitatively equal to that of vecuronium, but was slower in onset. The buffer solvent of midazolam 5 mg kg-1 did not change the steady-state blockade of vecuronium. Midazolam 5 mg kg-1 caused a shift to the left of the cumulative dose-response curves of vecuronium.

Animals↗