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Biomedical subjects

T B Vree

Publications and source records attributed to T B Vree.

At least 235 records · Page 13Linked to original sources
PubMed1985

Enoxacin decreases the clearance of theophylline in man.

In patients treated concurrently with theophylline and enoxacin, a new broad-spectrum antibacterial agent of the quinolone class, unexpectedly high plasma theophylline concentrations were measured. In part I of this study, daily plasma theophylline concentrations were measured in 14 patients. The mean +/- s.d. theophylline concentrations increased from 8.5 +/- 2.8 micrograms ml-1 prior to enoxacin to a maximum of 21.7 +/- 7.8 micrograms ml-1 during coadministration. In part II, six of these patients received aminophylline intravenously at a constant infusion rate and under controlled conditions. Plasma theophylline concentrations rose from 8.4 +/- 2.4 micrograms ml-1 prior to enoxacin treatment to 15.0 +/- 5.1 micrograms ml-1 at day 3 of coadministration (P less than 0.005). Plasma protein-binding and renal clearance of theophylline remained unchanged, whereas total body clearance of theophylline significantly decreased (P less than 0.005). From these observations it is concluded that the rise of plasma theophylline concentrations is caused by a reduced metabolic clearance of theophylline. If concomitant use of both drugs is necessary, monitoring of plasma theophylline concentration and adjustment of the theophylline dose is recommended.

Adult↗
PubMed1985

Disposition of sulfadimidine and its N4-acetyl and hydroxy metabolites in horse plasma.

The plasma disposition of sulfadimidine (SDM) and its metabolites N4-acetylsulfadimidine (N4-SDM), 6-hydroxymethyl-4-methyl-pyrimidine (SCH2OH) and 5-hydroxy-4,6-dimethyl-pyrimidine (SOH), was studied in three horses following intravenous administration of SDM at dose levels of 20 and 200 mg/kg in cross-over trials. The percentages of N4-SDM (0.58-0.90%), SOH (0.83-6.75%) and SCH2OH (0.38-0.71%) in plasma, expressed as a percentage of the total sulfonamide concentration, were small and their plasma concentrations were parallel with SDM from 4 h following administration. At high doses (200 mg/kg), the elimination half-life was slightly longer than at low doses (6.0, 10.5, 11.0 vs 5.0, 9.5, 9.5, respectively). The plasma protein binding was related to the dose; it was for the 20 and 200 mg/kg doses, respectively:SDM:61.5-73.3% and 50.5-52.1%; SOH: 47.1-71.0% and 36.7-39.5%, and for N4-SDM: 45.9-63.2% and 38.3-53.7%. The protein binding for SCH2OH, measured in samples obtained at the high dose level, ranged from 13.8 to 20.0%.

Animals↗
PubMed1985

Relevance of serum protein binding of cefoxitin and cefazolin to their activities against Klebsiella pneumoniae pneumonia in rats.

An experimental Klebsiella pneumoniae pneumonia in rats was used to study the effect of protein binding of cefoxitin and cefazolin on their therapeutic activity. Both cephalosporins were similar with respect to their antimicrobial activity against the K. pneumoniae in vitro, but they differed in their degree of protein binding, being 34% for cefoxitin and 89 to 93% for cefazolin in uninfected rats and 24 and 71 to 83%, respectively, in infected rats. Various doses of these agents were administered by continuous infusion, which started 5 h after bacterial inoculation and continued for 65 h. Antimicrobial response was evaluated with respect to the numbers of bacteria recovered from lung and blood at the end of treatment. An inhibitory effect of protein binding on the in vivo antimicrobial activity was demonstrated. Cefoxitin was therapeutically effective at a constant plasma level that reached the MIC. To obtain a similar effect with cefazolin the plasma level of that drug had to be increased to a concentration more than three times the MIC.

Animals↗
PubMed1985

The in vitro effects of benzodiazepines on the rat diaphragm. Structure-activity relationships.

The effect of three different subgroups of benzodiazepines on the indirectly evoked twitch tension was investigated in the in vitro rat phrenic nerve - hemidiaphragm preparation. Two effects were observed: an initial increase in twitch tension at lower concentrations with some benzodiazepines, and a concentration-dependent depression at higher concentrations with all benzodiazepines. Significant differences for these effects were observed among the three subgroups of benzodiazepines and additionally within the subgroup of the 1,4-benzodiazepine-2-ketones. Structural requirements for both effects were different. For the increase of twitch tension a --CH3 substitution at R1 and a --F substitution at R2' were beneficial. For the twitch depression an --OH substitution at R3 and a --C1 substitution at R2' were optimal. An interaction between substituents at different substitution sites occurred. The potency of twitch depression showed a good correlation with literature reports of pKa values and a poor-to-inverse correlation with lipophilicity indices. A benzodiazepines antagonist, Ro 15-1788, caused no change in twitch tension in the concentration range of the investigated benzodiazepines nor did it prevent the twitch depression caused by benzodiazepines.

Animals↗
PubMed1985

Interaction of some benzodiazepines and their solvents with vecuronium in the in vivo rat sciatic nerve-tibialis anterior muscle preparation.

Interaction studies between different injectable benzodiazepines and vecuronium, a non-depolarizing neuromuscular blocking drug, were performed in the rat in vivo sciatic nerve-tibialis anterior muscle preparation. The investigated doses were aimed to be "sedative" in the rat. A significant antagonism of a steady state depression of the twitch height induced by vecuronium was observed during approximately 10 min after i.v. injection of those benzodiazepines containing organic solvents in their formulations (diazepam, desmethyldiazepam, oxazepam, temazepam, lorazepam and lormetazepam). This antagonism is mainly due to propylene glycol, the main organic solvent for the poorly water-soluble benzodiazepines. After the initial antagonism, a potentiation of the vecuronium-induced depression occurred with some of these benzodiazepines (diazepam, desmethyldiazepam, temazepam and lormetazepam). Two water-soluble benzodiazepines, midazolam and flurazepam, caused a significant potentiation of the vecuronium-induced block. Important side-effects (blood pressure drop, convulsions, hematuria) were observed with the amount of propylene glycol present in the investigated formulation of lormetazepam.

Animals↗
PubMed1984

Effects of methoxy groups in the NI-substituent of sulfonamides on the pathways of elimination in man. The acetylation-deacetylation equilibrium and mechanisms of renal excretion of sulfisomidine, sulfamethomidine and sulfadimethoxine.

Sulfisomidine, sulfamethomidine, sulfadimethoxine and their corresponding N4-acetyl derivatives were administered to man. The percentages of acetylation and deacetylation and those of protein binding, the half-lives of elimination and the apparent and true renal clearance values were measured. No acetylation phenotype could be demonstrated in these compounds. Methoxy substitution in the NI-pyrimidine group of sulfisomidine affects predominantly the renal clearance value and mechanism of the parent compound but has no influence on the renal clearance of the N4-acetyl derivatives. The renal clearance value of sulfisomidine is 232 +/- 33 ml/min, of sulfamethomidine 21.60 +/- 16.4 ml/min and of sulfadimethoxine 10.87 +/- 10.44 ml/min. The renal clearance values of the corresponding N4-acetylsulfonamide derivatives are 314 +/- 91 ml/min, 342 +/- 63 ml/min and 202 +/- 65 ml/min respectively. Tubular reabsorption, caused by methoxy substitution in the NI-pyrimidine ring, lowers the rate of elimination and increases the half-life. The half-life of sulfisomidine is 8.5 +/- 0.5 h, of sulfamethomidine 27.8 +/- 5.3 h and of sufadimethoxine 34.6 +/- 10.4 h.

Acetylation↗
PubMed1984

Isolation and identification of 4-hydroxysulfamerazine and preliminary studies on its pharmacokinetics in dogs.

For the following compounds: sulfamerazine, 4- hydroxysulfamerazine , N4- acetylsulfamerazine , N4-acetyl-4- hydroxysulfamerazine , the following data are reported: biosynthesis in the dog, isolation, identification by MS and NMR, TLC (Rf values) and HPLC (capacity factors and molar extinction), half-life of elimination, metabolism, renal excretion and protein binding in dog. Dogs are unable to acetylate sulfamerazine, but eliminate predominantly by hydroxylation of the N1-substituent. Administered N4- acetylsulfamerazine is predominantly eliminated by deacetylation to sulfamerazine which in turn is hydroxylated. The renal clearances of sulfamerazine and N4- acetylsulfamerazine in the dog are identical. The renal excretion of both compounds proceeds by the passive processes of glomerular filtration and tubular reabsorption. 4- Hydroxysulfamerazine and its glucuronide have a higher renal clearance than sulfamerazine.

Animals↗
PubMed1984

Interaction between the renal excretion rates of beta 2-microglobulin and tobramycin in man.

The renal excretion rate of beta 2-microglobulin in man is 127 +/- 98 ng/min at alkaline urine pH (pH 7). Tobramycin, up to intravenous doses of 160 mg (2 mg/kg) does not increase the renal excretion rate of beta 2-microglobulin. Tobramycin must have less affinity than gentamicin for the tubular system for active reabsorption of amino groups containing organic compounds. Due to this reduced affinity tobramycin will be absorbed less by the proximal tubular cells, which may be one of the reasons for tobramycin being less toxic than gentamicin. beta 2-Microglobulin excretion can be used as a parameter for the relative binding affinity of aminoglycosides.

Adult↗
PubMed1984

Excretion rates of sulfamethoxazole and N4-acetyl-sulfamethoxazole by fresh water turtles Pseudemys scripta elegans.

Sulfamethoxazole and N4-acetylsulfamethoxazole are excreted by fresh water turtles Pseudemys scripta elegans in a biphasic mode, characterized half-lives of 5 and 100 min. Acetylation and deacetylation reactions cannot be detected below a dose of 50 mg/kg. The mass balance of the dose administered is incomplete, only 30 per cent of the dose can be recovered as parent compound and metabolite. The sulfonamides must be mainly excreted by the faeces and may be metabolized in the gastro-intestinal tract.

Acetylation↗
PubMed1984

In vitro interaction of diazepam and oxazepam with pancuronium and suxamethonium.

In vitro studies using the rat phrenic nerve-hemidiaphragm preparation were performed to investigate the effects of diazepam and three of its metabolites on indirectly evoked twitch tension. Diazepam, desmethyldiazepam and temazepam alone caused an increase in twitch tension in lower concentrations, followed by complete depression in higher concentrations. Oxazepam did not cause an initial increase in twitch tension, but showed an immediate and dose-dependent depression. Cumulative concentration-response curves for pancuronium and suxamethonium in the presence of different concentrations of diazepam or oxazepam showed that small concentrations of diazepam, which did not change twitch tension alone, caused antagonism of the action of pancuronium, but not of suxamethonium. With oxazepam no such antagonism was observed. In liminal and supraliminal concentrations, both diazepam and oxazepam potentiated the action of pancuronium and suxamethonium. Possible implications for in vivo interactions are discussed.

Animals↗
PubMed1984

Clinical pharmacokinetics of carbenicillin, carfecillin, ticarcillin and BL-P 1654 in dairy cows.

The minimal inhibitory concentrations (MIC) of carbenicillin, ticarcillin and BL-P 1654 for gram-negative udder pathogens were determined using the agar plate dilution method. The MIC of the drugs for 50% and 90% of the isolates examined ranged for Escherichia coli and Aerobacter spp. from 1.56 to 25 micrograms/ml, and for Klebsiella spp. and Pseudomonas spp. from 3.12 to 50 micrograms/ml. The Serratia spp. were relatively non-susceptible for the drugs studied (MIC greater than 50 micrograms/ml). Each drug was administered intravenously at 5 g and 15 g per cow to different groups of cows with normal and inflamed quarters of the udder. Distribution and elimination kinetic parameters calculated from serum drug level data were very similar to those of other beta-lactam antibiotics. Although drug concentrations in milk from inflamed quarters were higher than in milk from normal quarters, they were considerably below the MIC for the majority of gram-negative udder pathogens. The data suggest that parenteral treatment of gram-negative udder infections with carbenicillin, carfecillin, ticarcillin and BL-P 1654 at the dose levels used in the present study is unlikely to result in a bacteriological cure and would probably be clinically ineffective.

Animals↗
PubMed1984

Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation.

The effect of equimolar cumulative concentrations of 11 different benzodiazepines on the indirectly evoked twitch contraction was investigated in the rat in-vitro phrenic nerve-hemidiaphragm preparation. Depending on the pattern of the concentration-response curves two groups of benzodiazepines can be distinguished: (i) a first group with a biphasic action, e.g. potentiation of twitch tension in low concentrations and depression of twitch tension in high concentrations, and (ii) a second group with primary depression of twitch tension with increasing concentrations. All of the tested compounds ultimately caused a 100% depression of twitch tension at concentrations ranging from 0.175 to 0.35 mmol litre-1. Although this peripheral effect of benzodiazepines on neuromuscular function is not the main site of action of these compounds, there are enough arguments to state that it is not a simple toxic effect. There is some evidence from this study that the peripheral component of the benzodiazepine effect on muscle relaxation may involve a multi- rather than one single receptor system.

Animals↗
PubMed1984

Some pitfalls in selecting descriptive pharmacokinetic models.

Some pitfalls in selecting pharmacokinetic models are enumerated. To calculate the pharmacokinetic parameters of a drug that exhibits a biphasic convex plasma concentration-time curve, a two-compartment model does not automatically have to be applied. When only the parent drug in plasma is considered, a two-compartment model seems to be most appropriate. However, when the kinetic behavior of the metabolite has to be taken into account, and when a metabolic equilibrium underlies the metabolic elimination, the two-compartment model may not be appropriate. Also, when calculating the kinetic parameters of a drug with a concave biphasic plasma concentration-time curve, a capacity-limited metabolic conversion is not the automatic explanation for this observation. Limitations in renal excretion and bioavailability may be the reasons for this behavior. Convex and concave biphasic plasma concentration-time curves are illustrated, using sulfonamides as test compounds.

Crystallization↗
PubMed1984

Placental transfer of midazolam and its metabolite 1-hydroxymethylmidazolam in the pregnant ewe.

Plasma concentrations of midazolam and its metabolites were measured in maternal and fetal blood after intravenous administration of 90 mg of midazolam to seven pregnant ewes in whom sampling catheters had been chronically implanted. Midazolam and its metabolite 1-hydroxymethylmidazolam crossed the placenta of the pregnant ewe. The fetal/maternal plasma concentration ratio of midazolam and the metabolite was 0.15. The distribution and elimination half-lives of midazolam and the metabolite were identical in both maternal and fetal circulations. The major compound found in the urine was the metabolite 1-hydroxymethylmidazolam glucuronide.

Anesthesia, Obstetrical↗