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J M Turquais

Publications and source records attributed to J M Turquais.

5 recordsLinked to original sources

Transfer in vitro of three benzodiazepines across the human placenta.

A comparative study of the placental transfer to the foetus of three benzodiazepines was performed using a dual perfusion system of the human placental lobule. A transport fraction was calculated for each benzodiazepine and was compared with reference substances. Relative to antipyrine, the transport fraction of diazepam was 85%, and that of nordiazepam was 84%. The transport fraction of clorazepate represented only 20% of that of tritiated water. The relatively high transfer of diazepam and nordiazepam can be attributed to their high lipid solubility, and the lower transfer of clorazepate is due to its polar nature. It is suggested that in certain instances this benzodiazepine may be of especial value to obstetricians.

Anti-Anxiety Agents

Pharmacokinetics of clorazepate in pregnant and non-pregnant women.

A single dose of clorazepate 20 mg was injected i.m. in 7 pregnant and 7 non-pregnant women. Blood samples were collected for one week, and urine was collected for 24 h after the dose. The concentrations of clorazepate and its metabolite nordiazepam were determined by electron capture gas liquid chromatography. There was no difference between the two groups on physical examinations. Clorazepate was rapidly absorbed and the peak concentration was reached within 2 h. Mean pharmacokinetic parameters for clorazepate were absorption half life 0.77 h in pregnant women and 0.56 h in non-pregnant women; elimination half life 1.3 h in pregnant women and 2.0 h in non-pregnant women; volume of distribution: 0.43 1 . kg-1 in the pregnant women and 0.33 1 . kg-1 in non-pregnant women. Nordiazepam reached its peak concentration within 12 h after dosing; its mean half life of elimination was 180 h in pregnant women and 60 h in non-pregnant women. Within 24 h, 1.3% of the clorazepate was recovered in urine from pregnant women and 7% in urine from the non-pregnant women.

Adult

Pharmacokinetics of the placental transfer and distribution of clorazepate and its metabolite nordiazepam in the feto-placental unit and in the neonate.

Clorazepate 20 mg was given i.m. to 49 mothers during the first stage of labour. The elimination of the drug was studied in 27 newborns produced by these mothers. The same dose was given to 13 women who underwent amniocentesis and to 7 women who were breast-feeding. "Total nordiazepam", i.e. the sum of clorazepate and its metabolite nordiazepam, was determined by gas-liquid chromatography in maternal blood, umbilical cord blood (both arterial and venous), amniotic fluid and in milk. Clorazepate was found to cross the placental barrier slowly, but nordiazepam was transferred more rapidly. Nordiazepam was found in the milk and in the blood of neonates after breast-feeding had started.

Adult

[Determination of dipotassium clorazepate in the plasma by gas chromatography (author's transl)].

The authors present a method of estimation of dipotassium clorazepate by gas chromatography with a detector for electron capture. It requires 2 ml of blood. Two separate extractions are necessary, including one immediately after the sampling to determine the nordiazepam present at the time of the blood sample. The second extraction permits one to determine the total nordiazepam obtained by transformation of all the dipotassium clorazepate. This method is simple and rapid and permits one to determine with precision, specificity and good reproducibility (CV -- 3%) the therapeutic concentrations of this drug.

Anti-Anxiety Agents

Micromethod for determination of diazepam by electron-capture gas-liquid chromatography.

We used 100 microliters of plasma for the determination of diazepam. After the internal standard, prazepam, is added, the serum is directly extracted with diethyl ether, the extract is evaporated, the residue is dissolved in ethanol, and the drug is measured by gas-liquid chromatography, with use of an electron capture detector. With this procedure, 2.5 ng of diazepam in the sample can be speedily measured with specificity, accuracy, and reproducibility (CV = 4.5%).

Chromatography, Gas