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Biomedical subjects

T B Vree

Publications and source records attributed to T B Vree.

At least 145 records · Page 8Linked to original sources
PubMed1989

Continuous infusion of midazolam during anaesthesia and postoperative sedation after maxillofacial surgery.

The clinical effects and pharmacokinetics of 24 h infusion of midazolam (MDZ) during major maxillofacial surgery and postoperative observation in an Intensive Care Unit (ICU) were studied in 20 patients. During anaesthesia, infusion of MDZ at 5 mg/h combined with 67% nitrous oxide, 1.8 (s.d. = 0.8) mg of fentanyl, and 26.5 (s.d. = 11.4) mg of vecuronium, adequately suppressed clinical responses to surgical nociceptive stimuli. Postoperatively, infusion of MDZ was continued in the ICU at 5 mg/h until 9 a.m. of the first postoperative day for sedation of the intubated but spontaneously breathing patients. The depth of sedation in the ICU was scored from 1-5 (1 = "awake and tense", 5 = "unable to communicate"). During infusion the sedation score decreased from 3.8 after ICU arrival to 2.2 at 8 a.m. of the first postoperative day. Neither ventilatory nor circulatory depression were observed. After cessation of MDZ, recovery from sedation was fast. The degree of amnesia was low. During constant rate infusion no increase in plasma concentration of either MDZ or metabolites occurred. T1/2 beta of MDZ after cessation was 125 min (range 90-320) and its total body clearance was 10.5 ml/kg/min (s.d. = 3.1). The volume of distribution, clearance and T1/2 beta were significantly longer in women than in men. It was concluded that 24 h of MDZ infusion at 5 mg/h caused satisfactory ICU sedation with fast recovery, but that individual tailoring of the infusion rate may still improve the quality of sedation.

Adult↗
PubMed1989

Pharmacokinetics, metabolism, and renal excretion of articaine and its metabolite articainic acid in patients after epidural administration.

Articaine is metabolized into articainic acid. The half-lives of articaine are 0.54 +/- 0.05 and 2.44 +/- 0.30 h and that of its metabolite, 2.44 +/- 0.30 h. Of the administered dose approximately 2-5% is excreted unchanged, 40-70% is excreted as articainic acid, and 4-15% as articainic acid glucoronide. The percentage of the total dose recovered in the urine varies between 50% and 91%. Protein binding of articaine in patients varies between 50% and 70%, and that of articainic acid between 60% and 90%. Renal clearance of articaine varies between 12 and 28 ml min-1, while that of articainic acid is between 84 and 160 ml min-1.

Aged↗
PubMed1989

Comparison of the pharmacokinetics of intravenously administered rac-baclofen and its (-)-(R)- and (+)-(S)-enantiomers in dogs.

Baclofen is a centrally acting muscle relaxant marketed as the racemate. Since only the (-)-(R)-enantiomer is pharmacologically active, the pharmacokinetics of rac-baclofen and its enantiomers were studied individually in the same group of dogs to determine if there was any stereospecificity in the drug's kinetics after a single intravenous dose. High-pressure liquid chromatography was used to determine concentrations in plasma and urine. A major difference was found in the urinary recovery of the unchanged drug. Only about 50% of the dose of the clinically used racemate appeared as unchanged drug in the urine; whereas the active (-)-(R)-isomer was for the most part renally excreted (85%). Irrespective of isomeric composition, the renal clearance was dependent upon the creatinine clearance. Differences in non-renal clearance could not be explained by stereoselective formation of the gamma-hydroxymetabolite. It is concluded that in the dog, the active enantiomer is also pharmacokinetically preferred.

Animals↗
PubMed1988

The influence of ofloxacin and enoxacin on the metabolic pathways of theophylline in healthy volunteers. A pilot study.

The pharmacokinetic parameters of theophylline and its major metabolites were measured in two healthy volunteers, after the administration of theophylline alone and during co-medication with ofloxacin, 200 mg twice daily, or enoxacin, 200 mg twice daily. During enoxacin co-medication, elimination half-lives of theophylline increased from 8.7 h to 17.4 h and from 6.1 to 12.3 h, respectively. As the renal clearance of theophylline did not change, the decreased elimination of theophylline during enoxacin co-medication must result from a reduced metabolic clearance. Enoxacin co-medication caused a clearly decreased formation of the metabolites 1-methyluric acid and 3-methylxanthine, formed by N-demethylation, whereas the C-8 oxidation of theophylline was less influenced compared to the blank. Enoxacin's interference with the theophylline disposition is predominantly based on the inhibition of the microsomal N-demethylation. Ofloxacin co-medication did not induce a change in the plasma parameters or renal excretion of theophylline and its metabolites.

Adult↗
PubMed1988

Pharmacokinetics of nalidixic acid in man: hydroxylation and glucuronidation.

Nalidixic acid is metabolized by hydroxylation to 7-hydroxymethylnalidixic acid[[ and then by oxidation to 7-carboxynalidixic acid.[[ The half-lives of the two elimination phases of nalidixic acid are 0.75 and 2.5 h. The apparent half-lives of the metabolite 7-hydroxymethylnalidixic acid are 2.5 and 5.5 h. Plasma protein binding of nalidixic acid is 95% and that of 7-hydroxymethylnalidixic acid 65%. The renal clearance of nalidixic acid varies between 2 and 25 ml/min and that of 7-hydroxymethylnalidixic acid between 37 and 162 ml/min. Of nalidixic acid 42% is glucuronidated and 40% hydroxylated. Of the hydroxy metabolite 57% is glucuronidated and 32% excreted unchanged. 7-Carboxynalidixic acid is excreted in the urine and is not glucuronidated. The variations in the glucuronidation/hydroxylation ratio of nalidixic acid and the glucuronidation/renal excretion ratio of the 7-hydroxymethyl metabolite belong to a normal distribution.

Adult↗
PubMed1988

High-performance liquid chromatography of xanthines. Effects of N-methyl and C-8 hydroxyl substitution on the retention times.

The capacity factors of 26 xanthine derivatives were measured by reversed-phase high-performance liquid chromatography. N-Methyl substitution increased the capacity factor and the related lipid solubility. The descending order of the increase in capacity factor by the N-methyl group is: N-1 methyl greater than N-3 methyl greater than N-7 methyl greater than N-9 methyl. C-8 hydroxylation reduces the capacity factor in the xanthines. The reduction factor is 3.34 in xanthines with N-3 methyl substitution, 2.41 in xanthines with N-1 and/or N-7 methyl substitution and 1.68 in xanthines with N-9 methyl substitution.

Chemical Phenomena↗
PubMed1988

Pharmacokinetics of methotrexate in continuous ambulatory peritoneal dialysis.

The pharmacokinetics of methotrexate and its 7-hydroxy metabolite were studied in a patient undergoing continuous ambulatory peritoneal dialysis. A biphasic plasma-disappearance pattern of methotrexate was observed, with half-lives of 3.5 and 29 hours. The 7-hydroxy metabolite accumulated and showed a very slow rate of elimination, with an estimated final elimination half-life of over 120 hours. The mean peritoneal clearance rate of methotrexate was 0.13 l/h (range 0.05-0.20 l/h), dwell times significantly influenced the clearance rate. Strict monitoring of the methotrexate level, even after low doses, is necessary in continuous ambulatory peritoneal dialysis patients, to prevent serious bone marrow toxicity.

Adult↗
PubMed1988

Pharmacokinetics, renal clearance and metabolism of ciprofloxacin following intravenous and oral administration to calves and pigs.

The pharmacokinetics of ciprofloxacin, a quinoline derivative with marked bactericidal activity against gram-negative bacteria, was studied in calves and pigs following intravenous and oral administration. Ciprofloxacin was rapidly and well distributed in the body, exhibited a short elimination half-life of 2.5 h in both species, and was rapidly absorbed after oral administration (Tmax:2 to 3 h). The oral bioavailability in calves was 53 +/- 14% and for 1 pig 37.3%. The renal clearance of the unbound ciprofloxacin for both species was of the same order, indicated a predominantly tubular secretion pattern, and accounted for about 46% of the total drug elimination. No complete drug mass balance could be demonstrated. Small amounts of two metabolites were detected in the urine of calves, but not in pig urine.

Administration, Oral↗