A routine high-performance liquid chromatographic method for measuring midazolam in human serum has been developed. The sample preparation procedure consisted of simple liquid-liquid extraction with dichloromethane, followed by evaporation under nitrogen. The mobile phase used was a mixture of acetonitrile at 0.02 M and sodium acetate at pH 3.0 (80:20, v/v) and a flow-rate of 1.2 mL/min. The separation was performed on two cyanopropyl columns (150 x 4.6 mm). The detection was by UV absorption at 240 nm. A linear range from 10 to 1,000 ng/mL and a quantification limit of 7.4 ng/mL of serum was reached. The mean intra-assay and inter-assay reproducibility from serum sample spiked with 100 ng/mL were 4.1 and 4.7%, respectively. The recoveries from serum sample spiked with 50, 100, 500 ng/mL were 85.46, 85.38 and 85.57%, respectively. This method was developed to allow pharmacokinetics study of midazolam in young patients in short surgical interventions.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

Simultaneous determination of antidepressant drugs and metabolites by HPLC. Design and validation of a simple and reliable analytical procedure.

An analytical procedure suitable for routine use has been developed and validated for the simultaneous separation and quantification of most of the antidepressant drugs (bicyclic, tricyclic and tetracyclic) and their metabolites in human serum by reversed-phase high performance liquid chromatography with ultraviolet detection. The method has good sensitivity and specificity, without the need for long and complex extraction procedures. The results obtained with three different analytical columns were compared and an improvement in specificity by selection of column and detection wavelength used was achieved.

Amitriptyline↗

PubMedDate not supplied

Solid phase extraction and high performance liquid chromatographic determination of dobutamine in plasma of dialysed patients.

An isocratic reversed-phase high performance liquid chromatographic method has been developed for th e determination of dobutamine in the plasma of dialysed patients. A solid phase extraction method with a Sep-Pak C18 cartridge was used to isolate the drug and isoxsuprine (internal standard) from plasma. The separation was carried out on an ODS-Hypersil column with 0.1 M phosphate buffer:acetonitrile:methanol (72:20:8 v/v/v) as the mobile phase. The recovery of dobutamine added to plasma by the extraction procedure was 87 +/- 2.3% (mean +/- SD). The accuracy and reproducibility of the method were within acceptable limits over the concentration range 0-1000 ng/mL. Quantification was by fluorescence detection at 275 nm excitation and 310 nm emission wavelengths with a detection limit of 5 ng/mL for dobutamine. This procedure was applied to ascertain the pharmacokinetics of dobutamine infusion in nine patients with cardiogenic shock and end-stage renal disease undergoing haemodialysis.

Chemical Phenomena↗

PubMedDate not supplied

Contribution of scintigraphy to verify the reliability of different preparation processes for enteric coated capsules.

The aim of this work was to use radiopharmaceuticals such as technetium (99mTc) and indium (DTPA-Ca111In) to visualize, with a gamma-camera, the disintegration area and time of 3 types of enteric coated hard gelatin capsules (obtained by 3 different preparation processes) and thus, to verify that they are really resistant in gastric fluids and soluble in intestinal zones. Results are well correlated with those previously obtained in vitro (disintegration, dissolution) and in vivo (profiles of plasmatic concentrations versus time).

Acetaminophen↗

PubMedDate not supplied

Development of midazolam sublingual tablets: in vitro study.

Midazolam is a benzodiazepine with short elimination half-life, used as induction or continuous agent for general anesthesia. At present, only injectable solution is available from French hospital pharmacies. The aim of the study is the development of 5 mg midazolam sublingual tablets to realize a short general anesthesia without intravenous or intramuscular injection. Incorporation of citric acid in the tablet formulation leads to an increase of dissolution rates of active drug, but a decrease of diffusion through lipid membranes is observed with 10 mg of citric acid when using the Dibbern's Resomat three phases apparatus. One explanation of this result is that midazolam (pKa = 6.1) in presence of 10 mg of citric acid is ionised. The ionised form, more hydrophilic, cannot cross the artificial lipid membrane and therefore the diffusion decreases. On the other hand, the decrease of diffusion's rate, when pH increases, is explained by the precipitation of midazolam at pH higher than 6. A compromise between dissolution and diffusion results leads us to choose the sublingual formulation containing 5 mg of citric acid per tablet.

Administration, Oral↗

PubMedDate not supplied

Pharmacokinetics of midazolam: comparison of sublingual and intravenous routes in rabbit.

In France, the legal routes used to administer midazolam to a patient are intravenously and intramuscularly. For anaesthetists, these routes are not well adapted to paediatric use; they lead to pain at injection site and stress on children. The sublingual route should be a good compromise between stress and quick efficiency. We have developed a sublingual tablet of midazolam. The aim of the present investigation is to compare the pharmacokinetic parameters of midazolam tablets administered by the sublingual and intravenous routes in 6 rabbits to determine the bioequivalence between these routes. We have estimated the 1-hydroxy-midazolam serum level by difference between RRA and HPLC values. By the sublingual route, midazolam absorption is substantial and fast. The statistical analysis, on data obtained with HPLC dosage, shows no significant difference between pharmacokinetic parameter values calculated after intravenous and sublingual administration (0.5 mg). The absolute bioavailability was close to 100%. With RRA dosage, however, AUCs were greater than those obtained by HPLC dosage (174%). 1-hydroxy-midazolam seems to have a great importance in BZD activity. To estimate the bioequivalence between intravenous and sublingual midazolam administration, it is necessary to take into account the active metabolites.

Administration, Sublingual↗

PubMedDate not supplied

The possibilities of using the patellar tendon in the treatment of anterior cruciate ligament tears in children.

We describe a technique of reconstruction for complete midsubstance ruptures of the anterior cruciate ligament in patients with wide open physis, using the central third of the patellar tendon. This specific procedure is named the Clocheville technique. Results were very good in five cases and good in three cases at 2 years minimal follow-up. We neither noticed angular deformity, nor significant change in lower leg length. The Clocheville technique is an excellent alternative for young patients, with residual growth of the knee greater than 15 mm, if presenting an objective instability in activities of daily living or a proven meniscal tear that should be repaired.

Anterior Cruciate Ligament↗

PubMedDate not supplied

[Incidence of hyperuricemia and gout in coronary insufficiency from angina pectoris to myocardial infarct].

The authors try, on one hand, to estimate the role of hyperuricaemia and gout as risk factors in coronary diseases and, on the other, to decide whether the factors react in an isolated or associated fashion.

Adult↗

PubMedDate not supplied

[Coronary insufficiency in patients with gout].

Statistics on the frequency of coronary insufficiency in patients with gout are contradictory. Nevertheless, it is shown that a correlation often exists between attacks of gout and attacks of angina or acute ischaemic episodes. Finally, these anatomo-clinical studies prove the reality of the gouty heart if only because of the discovery of deposits of intracardiac urates.

Adenosine Diphosphate↗

PubMedDate not supplied

[Modification of uricemia coincident with myocardial infarct].

During myocardial infarction, uric acid values follow a very speciale evolutive curve, with 4 successive phases that might explain the occurrence of an episode of gout during an acute attack.

Female↗

PubMedDate not supplied

[100 cases of intra-epithelial epithelioma of the cervix uteri. Study of surgical specimens and results of treatment].

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Adult↗