Bioequivalence study comparing a new paracetamol solution for injection and propacetamol after single intravenous infusion in healthy subjects.

Objectives: A new, ready-to-use solution for injection of paracetamol (Perfalgan 10 mg/ml) without previous reconstitution has been developed. The aim of the study was to determine the serum concentration profiles of paracetamol after 15 min infusion of Perfalgan 0.5 g and 1 g doses and to demonstrate the bioequivalence between Perfalgan 1 g dose and a marketed reference formulation for injection, propacetamol 2 g (Pro-Dafalgan 2 g) equivalent to 1 g of paracetamol.

Capillary gas chromatographic method for the measurement of small concentrations of monoethylglycinexylidide and lidocaine in plasma.

The major metabolite of lidocaine, monoethylglycinexylidide (MEGX) is currently used as a dynamic marker of liver function. It has been proven, in recent advances, that the determination of MEGX formation after intravenous injection of lidocaine was an effective means of assessing liver dysfunction in critically ill patients. An accurate and sensitive gas chromatographic method has been developed for the determination of small quantities of MEGX formed in such cases.

Compound heterozygosity Hb S/Hb Hope (beta 136 Gly-->Asp): a pitfall in the newborn screening for sickle cell disease.

The presence of Hb Hope associated with Hb S may represent a pitfall (false positive) in the neonatal detection of sickle cell disease by two of the most widely used analytical methods in screening programmes-isoelectric focusing (IEF) and high performance liquid chromatography (HPLC). This example illustrates the need to improve analytical strategies to avoid unnecessary anxiety and summoning of families often from a cultural background in which testing of the father is difficult to obtain. It is suggested that using two independent HPLC procedures might improve the specificity of the screening strategies.

Acute-phase response, interleukin-6, and alteration of cyclosporine pharmacokinetics.

Objective: Administration of interleukin-6 partially reproduces the inhibitory effects of the acute-phase response on cytochrome P450-dependent drug metabolism. The aim of the study was to determine whether endogenous cytokine has such an effect in patients treated by cyclosporine, which is metabolized by the cytochrome P4503A subfamily.

Methods: Blood cyclosporine and serum interleukin-6 levels were determined in six patients undergoing bone marrow transplantation, as long as they received cyclosporine by continuous infusion.

Combination of long-acting furosemide and instant-acting amiloride: pharmacokinetics and pharmacodynamics in human subjects.

The pharmacokinetics and pharmacodynamics of the combination of amiloride (2 x 2.5 mg) and long-acting furosemide (2 x 10 mg) were compared with amiloride (5 mg) and furosemide (20 mg) in 12 healthy male volunteers aged 26.2 +/- 1.

[Treatment with sustained theophylline release. Monitoring by salivary assay in children].

We have tested the possibility of replacing plasma assays by salivary assays of theophylline for the monitoring of sustained-release theophylline therapy in asthmatic children. In a first group of 40 children aged 7.2 +/- 3.

[Application of a method of analysis using high performance liquid chromatography of isoniazid and acetylisoniazid to determine the phenotype of acetylation].

The described method is adapted from Moulin to measure plasma levels of isoniazid (INH) and acetylisoniazid (AINH) after extraction, HPLC separation and UV detection (254 nm). INH and AINH plasma levels of 109 patients aged between four months to 87 years were measured, allowing dosage individualization. The ratio of AINH to INH (Rm) three hours after administration was calculated.

Hemodynamic and pharmacokinetic study of propranolol and atenolol in cirrhosis patients.

The pharmacokinetic properties of propranolol and atenolol were evaluated both in 9 patients with cirrhosis and in 12 healthy subjects. The hemodynamic effects of the drugs were evaluated separately in the cirrhotic patients. Propranolol and atenolol significantly decreased wedged hepatic venous pressure and cardiac output in cirrhotic patients.

Comparison of changes in the characteristics of beta-adrenoceptors and responsiveness of human circulating lymphocytes during and after chronic administration of pindolol and propranolol.

The characteristics of the beta-adrenoceptors (3H-dihydroalprenolol binding) and the beta-adrenergic responsiveness (cyclic AMP response to isoproterenol) were studied in circulating lymphocytes from healthy volunteers before (D 0), on the 22nd day of treatment (D 22) and on the fifth day (D 30) following discontinuation of pindolol 15 mg/day or propranolol 160 mg/day. During pindolol therapy (D 22) the beta-adrenoceptor-affinity towards dihydroalprenolol was unchanged and the beta-adrenoceptor density decreased by 50%, an effect which persisted after drug administration ceased (D 30). The receptor "down-regulation" was accompanied by a parallel decrease in the maximal lymphocyte response to isoproterenol on D 22 and 30, by a shift to the right of the concentration-response curves to isoproterenol on D 22 and 30.