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A Frydman

Publications and source records attributed to A Frydman.

At least 19 recordsLinked to original sources
PubMed2006

Formation of a three-dimensional microstructure of Fe3O4-poly(vinyl alcohol) composite by evaporating the hydrosol under a magnetic field.

In this paper, we report on the self-assembly formation of three-dimensional microstructures of Fe3O4 hydrosol. First, we perform new, facile, and direct fabrication of a stable hydrosol of Fe3O4 nanoparticles, based on the sonolysis of an aqueous solution of iron acetate in the presence of PVA-100,000. This is then followed by investigations of the formation of different microstructures obtained on drying a drop of the water suspension on a glass microscope substrate. The evaporation was carried out both without and in the presence of an external magnetic field.

Crystallography, X-Ray↗
PubMed2005

Fabrication and magnetic properties of Ni nanospheres encapsulated in a fullerene-like carbon.

A very simple, efficient, and economical synthetic technique, which produces fascinating fullerene-like Ni-C (graphitic) core-shell nanostructures at a relatively low temperature, is reported. The thermal dissociation of Ni acetylacetonate is carried out in a closed vessel cell (Swagelok) that was heated at 700 degrees C for 3 h. The encapsulation of ferromagnetic Ni nanospheres into the onion structured graphitic layers is obtained in a one-stage, single precursor reaction, without a catalyst, that possesses interesting magnetic properties. The magnetoresistance (MR) property of Ni nanospheres encapsulated in a fullerene-like carbon was measured, which shows large negative MR, of the order of 10%. The proposed mechanism for the formation of the Ni-C core-shell system is based on the segregation and the surface flux formed in the Ni and carbon particles during the reaction under autogenic pressure at elevated temperature.

Carbon↗
PubMed2001

Synthesis and characterization of the antitumor activities of analogues of meridine, a marine pyridoacridine alkaloid.

Marine compounds with pyridoacridine skeletons are known to exhibit interesting antitumor activities. Among these compounds, meridine has already been reported as having significant antitumor activities in vitro. We synthesized 24 analogues of meridine substituted on ring A with the aim of obtaining compounds that display significantly higher in vitro antitumor activities than meridine. The 24 compounds and meridine used as a control compound were tested at 6 different concentrations on 12 different human cancer cell lines including various histopathological types (glioblastomas and breast, colon, lung, prostate, and bladder cancers). The IC(50) value (i.e., the drug concentration inhibiting the mean growth value of the 12 cell lines by 50%) of these 25 compounds ranged over 5 log concentrations, i.e., between 10 and 0.0001 microM, with four of the compounds exhibiting a significantly higher in vitro antitumor activity than meridine. These compounds will now be subjected to further pharmacological investigation including in vivo testing on both conventional murine tumors and human tumors grafted onto nude mice.

Alkaloids↗
PubMed2000

Effects of amphetamine and modafinil on the sleep/wake cycle during experimental hypersomnia induced by sleep deprivation in the cat.

Modafinil is a newly discovered waking substance now being used in the treatment of hypersomnia and narcolepsy. We have shown previously in the cat that, unlike amphetamine, modafinil induces long-lasting wakefulness (W) without behavioral excitation and subsequent sleep rebound, and that its waking effect does not depend on endogenous catecholamines. To further characterize the awakening properties of modafinil and current psychostimulants in experimental models of hypersomnia, we examined the effect of oral administration of placebo, modafinil (5 mg kg-1) or amphetamine (1 mg kg-1) on the sleep/wake cycle and power spectral density (PSD) in cats after an 18-h water-tank sleep deprivation period. We found that the placebo had no effect on the dynamics of sleep recovery, while both modafinil and amphetamine induced suppression of cortical slow activity and a waking state lasting 6-8 h. After the amphetamine-induced waking period, both deep slow wave sleep (SWS2) and paradoxical sleep (PS) occurred in greater amounts than after placebo and the PSD during SWS was also increased. Thus, the cumulative time spent in W during a 48-h period was similar to that with placebo, indicating enhanced sleep rebound. In contrast, after the modafinil-induced W, the occurrence and evolution of SWS2 or PS, as well as the PSD during SWS, were similar to those seen with placebo during the same period, so that the total time spent in W in a 48-h period remained significantly higher than the control level, indicating no additional sleep rebound. These results indicate that modafinil is effective against somnolence and hypersomnia and does not produce a subsequent increase in sleep and suggest that the pharmacological profile of modafinil is different from that of amphetamine.

Amphetamine↗
PubMed1996

Low-molecular-weight heparins: an overview of their pharmacodynamics, pharmacokinetics and metabolism in humans.

Low-molecular-weight heparins (LMWHs) comprise a group in the class of antithrombotic medications, a class headed by unfractionated heparin (UFH). The LMWHs, with mean molecular weights of 4.0-6.0 kD, differ in their individual manufacturing processes, the distribution of their fragment molecular weights, their in vitro potency (anti-Xa, antithrombin and anticoagulant activities) and, consequently, in their biodynamic patterns, recommended dose regimen, and efficacy/safety ratio. Their drug disposition profiles have been evaluated using two significant markers of their pharmacodynamic activity, namely anti-Xa and anti-IIa activities. Since they are mainly administered subcutaneously, then compared to UFH, they are almost completely absorbed (F > or = 90%) and, in contrast to UFH, those for which data are available in the literature exhibit linear pharmacokinetics with proportionality between anti-Xa (and anti-IIa in some cases) plasma concentration and dose, and stationary distribution volume and clearance processes when the dosage is increased. Their distribution volume is close to the blood volume, they are partially metabolized by desulphatation and depolymerization, but urinary excretion of anti-Xa activity for enoxaparin, dalteparin and nadroparin, all given at doses for prevention of venous thrombosis, is between 5 and 10% of the injected dose. However, these LMWHs differ in the extent of their non-renal clearance, resulting in different apparent elimination half-life values and relative apparent bioavailability. When considering certain at-risk situations, using doses for preventing thromboembolism, the LMWHs do not significantly cross the placenta of pregnant women and their excretion profiles are only slightly altered in severe (endogenous creatinine clearance less than 15 ml/min) renal disease patients when given at doses recommended for prevention of venous thromboembolism. Because of the differences among LMWHs, the clinical profile of a given LMWH cannot be extrapolated to another one or generalized to the whole LMWH family.

Aged↗
PubMed1995

Comparison of the pharmacokinetic profiles of three low molecular mass heparins--dalteparin, enoxaparin and nadroparin--administered subcutaneously in healthy volunteers (doses for prevention of thromboembolism).

The present trial was designed to comparatively investigate the pharmacokinetic profile and evaluate the apparent bioavailability pattern of three already marketed low molecular mass heparins (LMMHs): dalteparin (Fragmin), nadroparin (Fraxiparin), and enoxaparin (Lovenox) given by subcutaneous route. The study was carried out in 20 healthy young volunteers given, according to a cross over design, a single subcutaneous injection of the doses recommended for the prophylaxis of deep vein thrombosis (commercial preparations, prefilled syringes): dalteparin 2,500 IU (= 2,500 IU anti-Xa), nadroparin 7,500 ICU (= 3,075 IU anti-Xa), enoxaparin 20 mg (= 2,000 IU anti-Xa) and enoxaparin 40 mg (= 4,000 IU anti-Xa). Of the markers used, activated partial thromboplastin time (APTT), thrombin clotting time (TCT), Heptest, anti-thrombin (aIIa) activity and anti-Xa (aXa) activity, the most pertinent parameter (from a biodynamic viewpoint) is plasma aXa activity. We demonstrated that dalteparin, nadroparin and enoxaparin exhibit statistically significantly different pharmacokinetic and overall disposition patterns. Normalized to the same injected dose (1,000 IU aXa), the relative actual amount of plasma anti-Xa activity generated by enoxaparin is 1.48 times greater (p < 0.001) than that of nadroparin and 2.28 times greater (p < 0.001) than that of dalteparin while the plasma amount induced by nadroparin is 1.54 times greater (p < 0.001) than that of dalteparin. The apparent total body clearance of enoxaparin doses (CL/F = 16.7 +/- 5.5 and 13.8 +/- 3.2 ml/min) is significantly smaller than those of nadroparin (CL/F = 21.4 +/- 7.0 ml/min; p < 0.01) and dalteparin (CL/F = 33.3 +/- 11.8 ml/min; p < 0.001) while dalteparin apparent clearance is about 1.5-fold greater (p < 0.001) than that of nadroparin. These LMMHs also differ by their renal excretion pattern: more fragments exhibiting an anti-Xa activity are recovered in urine following enoxaparin doses (6.4 and 8.7% of the dose, respectively) than following nadroparin (3.9%) and dalteparin (3.4%) injection. These differences in the disposition profiles explain why the apparent elimination half life t1/2 values of the LMMHs compared here are different: dalteparin: 2.8 h; nadroparin: 3.7 h; and enoxaparin: 4.1 h. Whether or not these differences may contribute to explain the different safety/efficacy balance of each of these antithrombotic medications remains to be discussed and needs further studies.

Adolescent↗
PubMed1994

Pharmacokinetics of sparfloxacin in humans after single oral administration at doses of 200, 400, 600, and 800 mg.

The pharmacokinetics of sparfloxacin at oral doses of 200, 400, 600, and 800 mg were studied in 12 healthy volunteers in a randomized double-blind crossover study. Each dose administration was separated by a 1-week washout period. Plasma and urine samples were collected up to 120 hours postdosing, for determination of free and total (free plus glucurono-conjugated) sparfloxacin levels by high-performance liquid chromatography assay and ultraviolet detection. Mean Cmax values ranged from 705 +/- 158 to 1966 +/- 620 ng/mL for the 200 to 800 mg doses, at median tmax ranging from 4 to 5 hours. A slight decrease of sparfloxacin bioavailability with increasing dose was observed because AUC was 87% to 88% of the expected area when the dose was doubled. The elimination half-life values were constant over the dose range (with values ranging from 18 to 21 hours) as well as the renal clearance. The metabolic ratio conjugated/free drug was not modified by increasing dose.

Administration, Oral↗
PubMed1994

Aprikalim: radioimmunoassay and pharmacokinetic studies in mouse, monkey, and dog.

A stereoselective and specific radioimmunoassay (RIA) was developed for aprikalim (RP 52891), a novel potassium channel opener. Antibodies were produced in rabbits immunized with the pure levorotatory enantiomer (1R,2R) of the hapten derivative bearing an acid function at the end of the lateral chain and conjugated to bovine serum albumin. In displacement studies with the enantiomerically pure radioligand (radioiodinated tyrosine methyl ester conjugate of the hapten derivative), the opposite enantiomer showed only 0.1% cross-reaction. Negligible binding occurred when analogues or metabolites of aprikalim were tested for cross-reactivity. The detection limit was 0.25 ng/mL (9.31 x 10(-10) M) in a 20-microL plasma sample. The assay was used successfully to determine aprikalim pharmacokinetics in mice, monkeys, and dogs. Beagle dogs were given a 10 micrograms/kg intravenous (iv) bolus dose or 10 micrograms/kg iv bolus followed by 0.1 microgram/kg/min infused over 30 min (nonhypotensive doses which reduce myocardial infarct size significantly). The plasma concentrations declined monoexponentially with a mean overall elimination half-life of 1.53 h and a mean plasma clearance of 52 mL/min (5.1 mL/min/kg). A slow-release oral formulation produced a significant delay in the rate of absorption, a 4-fold decrease in the peak plasma level, and a 2-fold decrease in apparent oral bioavailability relative to that observed for an oral solution. A comparison of aprikalim pharmacokinetic parameters in mouse, monkey, and dog revealed great similarity in disposition characteristics in these species.

Animals↗
PubMed1994

Effect of diet on the single- and multiple-dose pharmacokinetics of sustained-release ketoprofen.

The indirect effect of diet on the single- and multiple-dose pharmacokinetics of sustained-release ketoprofen was studied in 16 healthy male volunteers. In an open, cross-over design, 200 mg ketoprofen was administered as a gastric-juice-resistant, sustained-release tablet once daily during two periods of 5 days. A low-calorie/low-fat diet (LCFD) was given in the first period and a high-calorie/high-fat diet (HCFD) in the second period. The first meal on each day was given 4 h after drug intake. Ketoprofen plasma concentrations were measured over 24 h after the first dose on day 1 and over 36 h after the final dose on day 5 of each period. On average, plasma concentrations of ketoprofen were higher with the LCFD than with the HCFD. With the HCFD there was a tendency to longer absorption-lag times on day 5. The maximum concentration and the area under the curve over one 24-h dosage period (AUC0-24) were significantly higher with the LCFD, both on day 1 and on day 5. For AUC0-24 the differences were on average 15% (day 1) and 24% (day 5). The same tendency was observed for the amount excreted in urine over 24 h (Ae), but the difference was only significant on day 1 (14%). The elimination rate constant (K beta) and the mean residence time were similar for the two diets, both on day 1 and on day 5. From these results, we conclude that there was an acute indirect effect of diet when a meal was had 4 h after intake of the medication.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Comparative effects of enoxaparin and unfractionated heparin in healthy volunteers on prothrombin consumption in whole blood during coagulation, and release of tissue factor pathway inhibitor.

In a randomized crossover study twelve healthy male volunteers (23.5 +/- of 4.8 years, 73.0 +/- 6.4 kg, 180.8 +/- 5.7 cm) received one subcutaneous injection of either enoxaparin (EN) at 40 mg or 1 mg kg-1, or unfractionated heparin (UH) at 5,000 IU at one week intervals. Area under curves (AUC) of Anti-Xa and Anti-IIa activities correlated with EN dose. The relative effectiveness of EN versus UH 5,000 U as assessed by AUC ratio (EN/UH) was 7 and 15 for Anti-Xa activity, 1.3 and 3.1 for Anti-IIa activity after sc injection of EN 40 mg (4,000 Anti-Xa IU and 1,200 Anti-IIa U) and 1 mg kg-1 (7,300 +/- 640 Anti-Xa IU and 2,190 +/- 290 Anti-IIa IU) respectively. In volunteers receiving EN, a dose dependent inhibition of thrombin generation rate in platelet depleted plasma (PDP), measured with a new and simple chromogenic thrombin generation assay, was observed when compared with baseline values. Similarly, intrinsic prothrombin activation in whole blood, evidenced by measuring residual factor II in serum 2 hours after clotting (prothrombin consumption test: PC), was inhibited in a dose dependent manner. In UH treated volunteers, although the inhibition of thrombin generation rate in PDP was similar to that observed with EN 40 mg, prothrombin consumption in whole blood was not significantly modified. Tissue factor pathway inhibitor (TFPI) activity release was increased similarly for UH and EN 40 (1.4 fold increase above baseline values) and 1.9 fold for the higher dose of EN. The discrepancy between prothrombin consumption in whole blood and inhibition of thrombin generation rate in PDP in the UH and not in the EN group strongly suggests that UH and not EN is influenced by the presence of a platelet component. This could be formed during thrombin induced platelet activation. Platelet factor 4 is a possible candidate. Another hypothesis involves the role of TFPI-UH complex anticoagulant activity which might be inhibited more during whole blood coagulation than the TFPI-EN complex.

Adult↗
PubMed1993

Secnidazole concentrations in plasma and crevicular fluid after a single oral dose.

Metronidazole and related nitroimidazole derivatives, including ornidazole and tinidazole, have been used successfully in the treatment of periodontal diseases. The purpose of this study was to measure secnidazole (another nitroimidazole derivative) concentrations in plasma and gingival crevicular fluid (GCF) after intake of a single oral dose. Secnidazole concentrations were estimated in 11 human healthy volunteers after a single dose of 2 g taken orally. Samples of blood and GCF were collected before intake and during the following 72 h. A high-performance liquid chromatography (HPLC) method has been developed for the determination of secnidazole in microsamples (1 to 3 microliters) of GCF. The mean peak blood and GCF levels were equal to 40.5 +/- 9.4 micrograms ml-1 at 2 h in blood and 26.4 +/- 7.0 micrograms ml-1 at 1 h in GCF, respectively. Apparent elimination half-life was 28.8 h (blood) and 30.4 h (GCF), respectively. These results show that the rate and extent-absorption of secnidazole are slightly higher in blood than in GCF, but the elimination of the drug is similar in the two body fluids.

Absorption↗
PubMed1992

Determination of Taxotere in human plasma by a semi-automated high-performance liquid chromatographic method.

A rapid, selective and reproducible high-performance liquid chromatographic (HPLC) method with ultraviolet detection was developed for the determination of the anti-cancer agent Taxotere in biological fluids. The method involves a solid-phase extraction step (C2 ethyl microcolumns) using a Varian Advanced Automated Sample Processor (AASP) followed by reversed-phase HPLC. The validated quantitation range of the method is 10-2500 ng/ml in plasma with coefficients of variation < or = 11%. The method is also suitable for the determination of Taxotere in urine samples under the same conditions. The method was applied in a phase I tolerance study of Taxotere in cancer patients, allowing the pharmacokinetic profile of Taxotere to be established.

Antineoplastic Agents, Phytogenic↗
PubMed1992

Body distribution of fully biodegradable [14C]-poly(lactic acid) nanoparticles coated with albumin after parenteral administration to rats.

Fully biodegradable polylactic acid (PLA) nanoparticles (90-250 nm) coated with human serum albumin (HSA) were prepared by high-pressure emulsification and solvent evaporation, using the protein as surfactant. A new analytical tool was developed, based on Mie's law and size exclusion chromatography, to establish that, after evaporation of the solvent, the protein saturates the surface of the nanoparticles, masking the PLA core. According to this technique, no HSA is encapsulated in the polymer matrix. A radiolabelled [14C]-PLA50 was synthesized to follow the fate of this new drug carrier after i.v. administration to rats. The time necessary to clear the albumin-coated nanoparticles from the plasma was significantly longer than for the uncoated ones but not extended enough to target cells other than mononuclear phagocytes. As deduced from whole-body autoradiography and quantitative distribution experiments, the 14C-labelled polymer is rapidly captured by liver, bone marrow, lymph nodes, spleen and peritoneal macrophages. Nanoparticle degradation was addressed following 14C excretion. The elimination of the 14C was quick on the first day (30% of the administered dose) but then slowed down. In fact, if the metabolism of the PLA proceeds to lactic acid which is rapidly converted into CO2 via the Krebs cycle (80% of the total excretion was fulfilled by the lungs), anabolism from the lactic acid may also have taken place leading to long-lasting radioactive remnants, by incorporation of 14C into endogenous compounds.

Animals↗
PubMed1992

A phase I, double-blind, placebo-controlled study of the tolerance and pharmacokinetic behaviour of RP 59500.

The tolerance and pharmacokinetic behaviour of a new injectable streptogramin antibiotic, RP 59500 were evaluated on 26 healthy male volunteers in a double-blind, placebo-controlled, phase I study. The doses used were 1.4, 2.8, 4.6, 7.0, 9.8, 12.6, 16.8, 22.4 and 29.4 mg/kg; each dose was administered as a 1 h infusion to eight subjects, two of them receiving placebo. Blood levels of RP 59500 were measured by both microbiological and HPLC assays. At the end of the infusion, Cmax for RP 59500 ranged from 0.95 +/- 0.22 to 24.20 +/- 8.82 mg/L. The apparent elimination half-life of the compound ranged from 1.27 to 1.53 h. RP 59500 did not significantly affect any of the laboratory or clinical assessments (blood pressure, pulse rate, ECG, peak expiratory flow rate). Reported adverse effects were of mild intensity; the most frequent event was mild pain or burning at the infusion site with doses of 7 mg/kg or higher. These results support further studies of RP 59500 in phase II clinical trials.

Adult↗
PubMed1992

Pharmacokinetic profile of nicorandil in humans: an overview.

Nicorandil is rapidly and almost completely absorbed from the gastrointestinal tract. Nicorandil is not metabolized significantly by the liver during passage through the portal system (lack of first-pass effect). Thus, it easily enters the systemic blood flow, resulting in almost complete bioavailability (75-100%). The concomitant food intake decreases the rate of absorption of the drug, resulting in a delay of peak plasma concentration, but has little or no effect on maximal plasma concentration or total amount of absorbed nicorandil. After oral administration of a 5-, 10-, 20-, or 40-mg dose, there is a linear relationship between the doses and increases of maximum plasma concentrations and area under the curve, demonstrating that the pharmacokinetics of nicorandil are linear. Steady-state plasma concentrations of nicorandil usually are reached within approximately 96-120 h after continuous dosing (20 mg b.i.d.), probably due to its distribution and metabolism patterns. On average, the Cmax then is approximately 300 ng/ml, which is achieved rapidly within 30 min after drug intake. Nicorandil is bound weakly to human albumin and other plasma proteins (approximately 25%). After oral (and i.v.) administration of the drug, the apparent volume of distribution is approximately 1.0 L/kg body weight. Nicorandil is metabolized extensively, and the major route of elimination is the kidney: Less than 2% of the dose is excreted through the biliary route. As a consequence, the parent drug is excreted poorly in urine (very low renal clearance), whereas 2-nicotinamidoethanol, a pharmacologically inactive denitrated metabolite, is the major nicorandil-related compound excreted in urine. The nicotinamide/nicotinic acid biotransformation pathway contributes to the accumulation of nicorandil and 2-nicotinamidoethanol (denitrated metabolite) during repeated dosing because of the saturable merging of nicotinamide/nicotinic acid derivatives (from the nicorandil metabolism) into the NAD/NADP endogenous pool of coenzymes. The apparent elimination half-life is short (approximately 1 h), and total body clearance is close to 1.15 L/min, which is lower than the liver blood flow. Especially during repeated dosing, a slower elimination process appears that is related to only approximately 10% of the amount of nicorandil found in plasma. Most of the nicorandil metabolites are excreted during the 24-h period after dosing, with the remainder excreted more slowly (as nicotinamide derivatives). The pharmacokinetics of nicorandil are not altered significantly in elderly persons and in patients who have chronic renal impairment or liver insufficiency. Furthermore, its disposition profile is not modified when concomitant drugs such as drug-metabolizing enzyme inducers or inhibitors are given.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1991

Influence of rifampin on the pharmacokinetics of pefloxacin.

Pefloxacin and rifampin are frequently associated in the antibiotic therapy of deep-seated, and especially bone-located, infections. The influence of rifampin, a potent drug metabolism enzyme inducer, on the pharmacokinetics of pefloxacin was studied in a randomized crossover trial involving eight young healthy male volunteers. Every volunteer received either pefloxacin alone (period A) or pefloxacin after a 10-day induction by rifampin (period B) given as a 900 mg daily oral dose, and both periods were separated by a 3-week washout period. During both periods, pefloxacin was given during 3 days as a 400 mg b.i.d. oral dose (six doses) followed by a 400 mg intravenous dose on the fourth day. The kinetics of pefloxacin are significantly influenced by rifampin: The minimum (12-hour) plasma concentration, area under the concentration-time curve, and elimination half-life decreased respectively from 4.26 +/- 1.57 to 2.70 +/- 1.00 mg/L, 78.91 +/- 22.82 to 57.81 +/- 16.69 mg.hr/L, 14.46 +/- 3.46 to 10.08 +/- 2.44 hours (p less than 0.05). The renal clearance of pefloxacin was unchanged, but the plasma clearance increased from 94.04 +/- 39.04 to 126.82 +/- 47.36 ml/min (p less than 0.05). The plasma clearance of N-demethyl and N-oxide metabolites were similar for both periods, but the cumulative renal excretion (0 to 96 hours) decreased significantly (p less than 0.01) for period B versus period A. This definite but moderate inductive effect of rifampin on the pharmacokinetics of pefloxacin does not suggest a dose modification of pefloxacin in therapeutic association with rifampin, but pefloxacin assay in plasma seems to be advisable.

Adult↗