Effects of N omega-nitro-L-arginine on total and segmental vascular resistances in developing lamb lungs.

To determine whether endothelium-derived nitic oxide (EDNO), like dilator prostaglandins, attenuates pulmonary vasomotor tone more in younger than in older newborns, we examined the effects of a nitric oxide synthase inhibitor, N omega-nitro-L-arginine (L-NA), on total and segmental pulmonary vascular resistance (PVR) in isolated blood-perfused cyclooxygenase-inhibited lungs of < 2-day-old (2D) and 1-mo-old (1M) lambs. Total PVR was determined both from steady-state pressure-flow curves and total pressure gradients (delta PT) measured at constant flow (100 ml.kg-1 x min-1).

Pharmacokinetics of diacerein in patients with liver cirrhosis.

The pharmacokinetics of diacerein following a single oral dose of 50 mg was studied in 12 healthy volunteers, 10 patients with a mild liver cirrhosis (Child Pugh's grade A), and 6 patients with a more severe liver cirrhosis (Child Pugh's grade B to C). Statistical analysis using a Kruskal-Wallis test showed no significant differences between the three groups for the following parameters: median Cmax was 3.9 mg l-1 for the cirrhotic patients group I (CPI) and 3.

Nitrone spin-traps block calcium channels and induce pulmonary artery relaxation independent of free radicals.

Free radicals react with nitrones to form stable nitroxides which can be identified by ESR spectroscopy. Unfortunately, little is known regarding the pharmacological properties of these compounds. In this study, three commonly used nitrones, 5,5-dimethylpyrroline-N-oxide (DMPO), alpha-phenyl-tert-butylnitrone (PBN), and alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), were found to induce relaxation of preconstricted isolated rat pulmonary artery rings.

Pharmacokinetics and bactericidal activities of one 800-milligram dose versus two 400-milligram doses of intravenously administered pefloxacin in healthy volunteers.

Pefloxacin pharmacokinetics and serum bactericidal activities (SBA) against Escherichia coli and Staphylococcus aureus were compared after intravenous infusion of either a single 800-mg dose or twice-daily 400-mg doses into 16 healthy volunteers. Plasma pefloxacin concentrations were measured for up to 60 h, and SBAs were determined 1, 12, and 24 h after the start of the infusion. The mean areas under the concentration-versus-time curve for plasma were not different (138 versus 136 h.

Cefotiam concentrations in the sinus fluid of patients with chronic sinusitis after administration of cefotiam hexetil.

Cefotiam hexetil is a prodrug of cefotiam. The concentrations of cefotiam in plasma and sinus secretions were determined in 18 patients (10 males, 8 females, aged 39.3 +/- 13.

NG-monomethyl-L-arginine paradoxically relaxes preconstricted canine intrapulmonary arteries.

We studied the effects of NG-monomethyl-L-arginine (LMMA), a nitric oxide (NO) synthesis inhibitor, in canine intrapulmonary arteries constricted with phenylephrine. Isolated vessels were suspended in organ chambers containing modified Krebs solution, and isometric tensions were recorded. In contrast to the expected constriction predicted from other studies, LMMA instead caused dose-dependent vasorelaxation in phenylephrine-constricted canine pulmonary arteries.

Hypoxia reduces potassium currents in cultured rat pulmonary but not mesenteric arterial myocytes.

To explore possible mechanisms underlying hypoxia-induced pulmonary vasoconstriction, the effect of hypoxia on outward K+ current (Iout) was evaluated in primary cultured rat pulmonary (PA) and mesenteric (MA) arterial smooth muscle cells using the whole cell patch-clamp technique. When the cells were bathed in standard physiological salt solution and the patch pipettes contained Ca(2+)-free media with 10 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), virtually all of the Iout, including both the rapidly inactivating component (Irt) and the steady-state (noninactivating) component (Iss), was mediated by voltage-gated K+ channels. Reduction of O2 tension in the bath solution from 155 Torr to < 74 Torr with sodium dithionite reversibly inhibited both Irt and Iss in PA myocytes, but not in MA myocytes.

Ionic currents in rat pulmonary and mesenteric arterial myocytes in primary culture and subculture.

The electrophysiological properties of cultured single vascular smooth muscle (VSM) cells from rat pulmonary (PA) and mesenteric (MA) arteries were studied using the whole cell patch-clamp technique. Cells were studied at 3-7 days as primary cultures, or were replated after 10-20 days and subcultured for 2-5 days. In the standard physiological bath solution (containing 1.

[Value of the theory of the optimal sampling scheme for bioequivalence studies].

Use of optimal sampling theory (OST) in pharmacokinetic studies allows a large reduction of the number of sampling times without loss in parameter estimation precision. OST has been applied to the determination of bioavailability parameters [area under the curve (AUC), maximal concentration (Cmax), time to reach maximal concentration, (Tmax)]. Three different Monte-Carlo simulations in twelve subjects have been performed, corresponding to different pharmacokinetic models: one-compartment with or without a lag time, two-compartment.

[Review and use of decision rules for bioequivalence trials].

To declare bioequivalent two different formulations of one active drug, bioavailability studies are conducted, usually based on area under the plasma concentration-time curves and peak concentrations. The decision follows a statistical basis with right statement of the hypotheses of bioequivalence that are described. This procedure allows to control the consumer risk of falsely accepting bioequivalence while minimizing the new formulation risk of erroneously rejecting bioequivalence.

Influence of renal function on the pharmacokinetics of diacerein after a single oral dose.

The pharmacokinetics of diacerein (a new anti-inflammatory analgesic antipyretic drug) following a single oral dose of 50 mg was studied in 12 healthy volunteers and two groups of eight patients with mild or severe renal insufficiency. Statistical analysis using a Kruskal-Wallis rank sum test showed a significant difference between the three groups for the following parameters. In severely uraemic patients, median AUC0-infinity was multiplied by a factor of ca 2: 40.

[Luminescence and detection in liquid chromatography. I: Change of environment of analytes].

The emissions of light by biorganisms or these obtained by alchemists were known since long time ago but the are used in analytical chemistry only when STOKES discovered that the intensity of this light was proportional to the quantity of the matter. The very large sensibilities reached, associated with the great separation's ability of the liquid chromatography allows to develop new processes for quantification of very low concentrations of luminescent or no luminescent molecules. Many pharmaceutical, biological toxicological environmental or alimentary applications show that it is possible in liquid chromatography to obtain a detection limit about the pico or femtomole when simple chemical process are used: direct potentialization of luminescence by addition of modifiers of the chemical environment of the analytes: solvents, cyclodextrins, surfactants, metallic ions, indirect potentialization of the luminescence by transfer of energy from an excited molecule: sensitized fluorescence and phosphorescence, excitation of the molecule by a chemical reaction or chemiluminescence.

[Luminescence and detection in liquid chromatography. II--Energy transfer from a stimulated molecule: indirect potentialization or sensitized luminescence].

Under the words of sensitized luminescence, the processes who include the transfers of energy from a donor to an acceptor are described. They are to the origin of new possibilities of detection in liquid chromatography by emission or inhibition of phosphorescence and fluorescence. These news technologies are illustrated by examples in pharmaceutic, biologic or food applications.

Pharmacokinetics of ibuprofen enantiomers after single and repeated doses in man.

The pharmacokinetic parameters of ibuprofen enantiomers after a single 600 mg dose and repeated 3 x 400 mg doses of Nurofen were determined in 12 healthy volunteers. Terminal half-lives were similar for both enantiomers, but plasma levels of S-ibuprofen were higher than those of R-ibuprofen, due to the chiral inversion and differences in distribution and metabolism. Comparison of maximal concentrations and areas under the concentration vs time curves between the first and last doses for each enantiomer indicated linear pharmacokinetics with no time-dependency.

Pharmacokinetics and absolute rectal bioavailability of hydrocortisone acetate in distal colitis.

The hydrocortisone pharmacokinetic profiles of hydrocortisone acetate foam (Proctocort) administered rectally was assessed in healthy volunteers and patients with ulcerative colitis or X-irradiation colitis. Endogenous production of hydrocortisone was suppressed by dexamethasone. Comparison of these data with those obtained after intravenous administration enabled assessment of absolute bioavailability, which was 30.

Endothelin-1-induced pulmonary arterial dilation is reduced by N omega-nitro-L-arginine in fetal lambs.

Endothelin-1 (ET-1) is a pulmonary vasodilator in the unventilated fetal lamb. The site and mechanism of this vasodilator response were investigated in isolated blood-perfused lungs from nine fetal lambs delivered at 127-140 days gestation. The vascular occlusion technique was used to partition the total pulmonary pressure gradient into pressure gradients across large and small arteries (delta PLA and delta PSA, respectively) and veins (delta PV).

In vitro kinetics of 8-methoxypsoralen penetration into human lymphoid cells.

Extracorporeal photochemotherapy (ECPC) requires ex vivo UVA irradiation of blood lymphocytes during the time of the theoretical peak 8-methoxsalen (8-MOP) concentration. The aims of this study were to determine the mechanism of cellular uptake of 8-MOP, its possible saturation and the time needed to reach maximal concentration (Tmax) in lymphoid cells. 8-MOP was measured by liquid chromatography in the supernatant of lymphoid cell suspensions incubated with a known amount of 8-MOP.

In vivo effects of amiodarone on cardiac beta-adrenoceptor density and heart rate require thyroid hormones.

To assess if the anti-beta-adrenergic effect and the bradycardia induced by amiodarone were mediated by thyroid hormone, we investigated these effects of amiodarone in euthyroid and hypothyroid rats. We studied control rats, thyroidectomized rats, control rats treated with amiodarone (50 mg/kg for 8 days), and thyroidectomized rats treated with amiodarone. At the end of the treatment, free thyroid hormone levels (FT4 and FT3) were determined, and cardiac beta-receptor density (Bmax) and affinity (Kd) were assayed by using (-)-[125I]iodocyanopindolol as radioligand.

Sensitive determination of josamycin and rokitamycin in plasma by high-performance liquid chromatography with fluorescence detection.

Rokitamycin and josamycin were successfully derivatized with dansylhydrazine in 20 min at 60 degrees C. Rokitamycin and josamycin levels were determined in plasma after ion-pair extraction into hexane-isoamyl alcohol with lauryl sulphate and precolumn derivatization. Resolution was obtained by liquid chromatography with fluorescence detection (352/537 nm) in 12 min.

Ontogeny of neonatal pulmonary vascular pressure-flow relationships.

Previously we reported that pulmonary vascular pressure gradients determined by vascular occlusion varied as a function of neonatal age. The purpose of this study was to evaluate the effect of blood flow on pressure gradients during normoxia (inspired O2 28%) and hypoxia (inspired O2 4.2%) in isolated, indomethacin-treated lungs obtained from lambs at less than 1, 2-4, 12-14, and 30-32 days of age (n = 6 at each age).

Pharmacokinetics of glafenine and glafenic acid in patients with cirrhosis, compared to healthy volunteers.

Pharmacokinetic parameters were evaluated in 12 patients with alcoholic cirrhosis and 12 healthy volunteers after a single 400 mg oral dose of glafenine. Glafenine (G) and its major active metabolite glafenic acid (GA) were measured at regular intervals using a specific high performance liquid chromatographic method. Glafenine absorption was significantly delayed in cirrhotic patients (CP) (Tmax = 2.

Pharmacokinetics of vidarabine in the treatment of polyarteritis nodosa.

The pharmacokinetics of vidarabine were studied in 8 patients with polyarteritis nodosa related to hepatitis B virus infection. The drug was administered by continuous infusion for three weeks at doses of 15 (1 week) and 7.5 (2 weeks) mg/kg per day, during which time 15 plasma exchanges were performed.

Bactericidal activity of daptomycin against vancomycin-resistant Enterococcus faecium in an in vitro pharmacokinetic model.

A dynamic in vitro model was used to determine the killing kinetics of daptomycin against 15 vancomycin-resistant clinical isolates of Enterococcus faecium. Concentration profiles simulating those observed in serum following administration of both low-dose (2 mg/kg) and high-dose (6 mg/kg) daptomycin were bactericidal within 5.5 and 2.

Diclofenac, paracetamol, and vidarabine removal during plasma exchange in polyarteritis nodosa patients.

Since plasma exchange (PE) represents a major treatment for patients suffering from systemic diseases, its influence on the kinetics of three drugs was investigated: vidarabine, used in patients with polyarteritis nodosa associated with hepatitis B virus (eight subjects), and diclofenac and paracetamol for investigative purposes (five subjects). This study confirmed that vidarabine is so rapidly deaminated to form hypoxanthine arabinoside (Hx-Ara) that no detectable concentrations were measured. Hx-Ara levels were used to evaluate vidarabine kinetics; 19.