Biomedical subjects

D R Morel

Publications and source records attributed to D R Morel.

93 records · Page 6Linked to original sources

PubMedDate not supplied

Pharmacokinetics of pipecuronium in infants, children and adults.

In order to explain the reported shorter clinical duration of action of cumulative ED95 of pipecuronium in infants as compared to children or adults, the pharmacokinetic profiles of pipecuronium were compared in infants (n = 6; mean age 6.8 months; mean weight 7.3 kg) in children (n = 6; mean age 4.6 years; mean weight 19.2 kg) and in adults (n = 7; mean age 42 years; mean weight 58.2 kg). Equipotent doses (2 x ED95) of pipecuronium were injected i.v. as single bolus and arterial blood was sampled for 4-5 h. Pipecuronium was quantified by complex formation with [125I]-labelled rose bengal. Pharmacokinetic parameters were calculated using a two-compartment open model. The median for the distribution half-life of pipecuronium was 2.54 min (interquartile range: 1.0-2.5 min) in infants and 2.04 min (0.26-2.04 min) in children; both were significantly shorter than in adults (5.75 [3.7-9.7] min). The plasma clearance of pipecuronium was significantly decreased in infants (1.50 [0.6-1.5] ml.min-1.kg-1; P < 0.05) as compared to children and adults (2.27 [0.88-2.27] and 2.45 [1.7-3.2] ml.min-1.kg-1, respectively). The total volume of distribution was similar in all three groups. We conclude that the pharmacokinetic features of pipecuronium are age-dependent: differences as compared to adults consisted of a faster distribution in both infants and children and a slower elimination in infants. The pharmacokinetic profile of pipecuronium does not explain the faster recovery from neuromuscular blockade in infants as compared to children. Because of the low total plasma clearance in infants, pipecuronium dosage should be carefully monitored to avoid accumulation and prolonged paralysis.

Adolescent↗

PubMedDate not supplied

Pharmacokinetics of atracurium besylate in the pig after a single i.v. injection.

A pharmacokinetic study of atracurium besylate was performed in the pig after a single i.v. bolus injection of 2 mg/kg, the dose needed to produce surgical neuromuscular blockade. The plasma concentration values were obtained by high performance liquid chromatography. Using a two-compartment pharmacokinetic model, the elimination half life was found to be 28.6 +/- 6.3 min (mean +/- SEM), the total volume of distribution 341 +/- 56 ml/kg and the plasma clearance 8.7 +/- 1.1 ml/min/kg. Although the doses required to obtain a satisfactory neuromuscular blockade as well as the plasma level, volume of distribution and plasma clearance values were higher in the pig than in man, the distribution and elimination half-lives were similar to those recently reported.

Animals↗

PubMedDate not supplied

An improved method for isolation of microvascular endothelial cells from normal and inflamed human lung.

Microvascular endothelial cells (MVEC), which differ from large vessel endothelial cells, have been isolated successfully from lungs of various species, including man. However, contamination by nonendothelial cells remains a major problem in spite of several technical improvements. In view of the organ specificity of MVEC, endothelial cells should be derived from the tissue involved in the diseases one wishes to study. Therefore, to investigate some of the immunopathological mechanisms leading to acute respiratory distress syndrome (ARDS), we have attempted to isolate lung MVEC from patients undergoing thoracic surgery for lung carcinoma and patients dying of ARDS. The method described here includes four main steps: (1) full digestion of pulmonary tissue with trypsin and collagenase, (2) aggregation of MVEC induced by human plasma, (3) Percoll density centrifugation, and (4) selection and transfer of MVEC after local digestion with trypsin/EDTA under light microscopy. Normal and ARDS-derived lung MVEC purified by this technique presented contact inhibition (i.e., grew in monolayer), and expressed classical endothelial markers, including von Willebrand factor (vWF), platelet endothelial cell adhesion molecule 1(PECAM-1, CD31), and transcripts for the angiotensin converting enzyme (ACE). The cells also formed capillarylike structures, took up high levels of acetylated low-density lipoprotein (Ac-LDL), and exhibited ELAM-1 inducibility in response to TNF. Contaminant cells, such as fibroblasts, smooth muscle cells, or pericytes, were easily recognized on the basis of morphology and were eliminated by selection of plasma-aggregated cells under light microscopy. The technique presented here allows one to study the specific involvement and contribution of pulmonary endothelium in various lung diseases.

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