Co-axis digital holography based on sinusoidal phase modulation using generalized lock-in detection.

Sinusoidal phase modulating (SPM) interferometers are used to precisely measure complex light fields with simple interferometric setups. Recently, a generalized lock-in technique has been proposed for optimizing the signal extraction in phase-modulated interferometers. This article shows its applicability in digital holography as well as digital holographic interferometry.

Plasmonic mode interferences and Fano resonances in Metal-Insulator-Metal nanostructured interface.

Metal-insulator-metal systems exhibit a rich underlying physics leading to a high degree of tunability of their spectral properties. We performed a systematic study on a metal-insulator-nanostructured metal system with a thin 6 nm dielectric spacer and showed how the nanoparticle sizes and excitation conditions lead to the tunability and coupling/decoupling of localized and delocalized plasmonic modes. We also experimentally evidenced a tunable Fano resonance in a broad spectral window 600 to 800 nm resulting from the interference of gap modes with white light broad band transmitted waves at the interface playing the role of the continuum.

Clinical pharmacokinetics of telithromycin, the first ketolide antibacterial.

Telithromycin is the first ketolide, which is a new class of antibacterial agents related to the macrolides that have structural modifications permitting dual binding to bacterial ribosomal RNA so that activity is retained against Streptococcus pneumoniae with macrolide-lincosamide-streptogramin(B) resistance. Clinical experience in infectious patients has shown that oral telithromycin 800mg once daily for 5-10 days is effective for the treatment of community-acquired upper and lower respiratory tract infections. Absorption of telithromycin in humans is estimated to be > or = 90%.

Effect of ketoconazole on the pharmacokinetics and safety of telithromycin and clarithromycin in older subjects with renal impairment.

Objective: The objective of this study was to determine the effect of multiple impairments in drug elimination on the pharmacokinetics and pharmacodynamics (effect on QTc interval), using clarithromycin as a comparator.

Methods: Thirty-two subjects aged > or = 60 years with renal impairment who were otherwise medically stable were recruited into this parallel-group study. Following stratification according to creatinine clearance (CL(CR)), subjects were randomized to a five-day treatment with ketoconazole (400 mg once daily) alone, or a five-day treatment with ketoconazole (400 mg once daily) and telithromycin (800 mg once daily) given concomitantly or a five-day treatment with ketoconazole (400 mg once daily) and clarithromycin (500 mg twice daily) given concomitantly.

Effects of itraconazole or grapefruit juice on the pharmacokinetics of telithromycin.

Study Objective: To determine whether coadministration of the cytochrome P450 3A4 (CYP3A4) inhibitors itraconazole or grapefruit juice will modify the pharmacokinetic profile of telithromycin, and to assess the safety of telithromycin.

Design: Two single-center, open-label studies; the itraconazole study was nonrandomized, sequential, and multiple dose, and the grapefruit juice study was randomized, two-period crossover, and single dose.

Setting: Two clinical investigative centers in the United States.

Pharmacokinetics and safety of the ketolide telithromycin in patients with renal impairment.

The pharmacokinetics and safety of the ketolide telithromycin were evaluated in two separate studies after single and repeat oral dosing in patients with varying degrees of renal impairment and in subjects with normal renal function. The single-dose study was an open-label, nonrandomized, parallel-group design in which all 40 patients received a single oral dose of telithromycin 800 mg. The repeat-dose study was an open-label study with a randomized, balanced, incomplete three-block treatment crossover design.

Pharmacokinetics of the ketolide telithromycin after single and repeated doses in patients with hepatic impairment.

The pharmacokinetic profiles of single and repeated oral doses of telithromycin 800 mg/day were compared in patients with hepatic impairment and healthy subjects in two open-label, non-randomized, parallel-group, multicentre studies. The maximal plasma concentrations (Cmax) and the area under the plasma concentration-time (AUC) curves for telithromycin were similar in hepatically impaired patients and healthy subjects in the single- and repeated-dose studies. The extent of formation of RU 76363, the major circulating metabolite of telithromycin, was decreased following single and repeated doses in patients with hepatic impairment compared with healthy subjects.

Lack of effect of food on the bioavailability of a new ketolide antibacterial, telithromycin.

Telithromycin is an innovative antibacterial designed for the treatment of community-acquired respiratory tract infections. This study assessed the effect of food on the bioavailability of a single oral dose of telithromycin 800 mg in healthy male subjects. Male volunteers aged 18-45 y were recruited for an open-label, single-dose, 2-period, cross-over study.

Pharmacokinetics and absolute oral bioavailability of an 800-mg oral dose of telithromycin in healthy young and elderly volunteers.

Background: This two-way, randomized, single-dose, crossover study determined the pharmacokinetics and absolute oral bioavailability of telithromycin in young and elderly healthy subjects.

Methods: Twelve young (18-40 years) and 12 elderly (>65 years and View Article and Find Full Text PDF

The pharmacokinetics and pharmacodynamics of enoxaparin in obese volunteers.

Objectives: The objective of this study was to compare the pharmacokinetics of the low-molecular-weight heparin enoxaparin in obese and nonobese volunteers, by means of two administration regimens.

Methods: Enoxaparin was administered subcutaneously (1.5 mg/kg once daily for 4 days) and in a single 6-hour infusion (1.

Evaluation of nanostructured carbonated hydroxyapatite coatings formed by a hybrid process of plasma spraying and hydrothermal synthesis.

Carbonated hydroxyapatite (CHA) coatings on a titanium alloy were prepared by hydrothermal synthesis of precursors plasma-sprayed with brushite as a raw powder. The structures, residual stresses, and bond strengths of the precursors and CHA coatings were investigated. The results showed that the sprayed precursors consisted of beta-Ca(2)P(2)O(7), alpha-Ca(3)(PO(4))(2), and CaHPO(4), whereas the CHA coatings exhibited a unique phase construction, nanostructured and needle-like crystals, and a fairly low tensile residual stress.

Population pharmacokinetics and pharmacokinetic-pharmacodynamic relationships for docetaxel.

The population approach has been implemented prospectively in the clinical development of docetaxel (Taxotere). Overall 640 patients were evaluable for the population PK/PD analysis. The PK analysis evidenced significant covariates explaining the inter-patient variability of docetaxel clearance and the PK/PD analysis demonstrated that the variability in clearance was a significant predictor of several safety endpoints.

Multiple-dose pharmacokinetics and safety of two regimens of quinupristin/dalfopristin (Synercid) in healthy volunteers.

Quinupristin/dalfopristin (Q/D) is a novel streptogramin antibiotic for the treatment of severe gram-positive infections. The purpose of this open, nonrandomized, parallel-group, phase I trial was to evaluate Q/D pharmacokinetics after single and repeated doses under the two different dosing regimens corresponding to the effective doses and to evaluate tolerability. Two groups of 10 healthy volunteers received multiple 1-hour intravenous infusions of 7.

Pharmacokinetics of quinupristin/ dalfopristin in patients with severe chronic renal insufficiency.

Objective: To compare the pharmacokinetic profile of a single intravenous injection of quinupristin/dalfopristin, a new injectable streptogramin, in healthy young individuals and patients with severe chronic renal insufficiency. A secondary objective was to assess the relative tolerability of this dose in these patients compared with healthy individuals.

Patients And Participants: 13 patients with severe chronic renal insufficiency (creatinine clearance 6 to 28 ml/min/1.

Pharmacokinetics of ketoprofen syrup in small children.

Ketoprofen is a nonsteroidal anti-inflammatory drug with analgesic, anti-inflammatory, and antipyretic properties. Its pharmacokinetics has not been determined in small children. The objective here was to determine the pharmacokinetics of ketoprofen syrup, 0.

A comparison of the pharmacokinetics and tolerability of riluzole after repeat dose administration in healthy elderly and young volunteers.

The pharmacokinetics and tolerability of the novel antiexcitatory agent, riluzole, were compared in 18 healthy elderly and 18 healthy gender- and weight-matched young volunteers. All participants received riluzole 50 mg twice daily (the recommended dosage for patients with amyotrophic lateral sclerosis), administered orally for 5 days. The pharmacokinetics of riluzole, determined on the morning of the 5th day of dosing, were not significantly affected by age or gender.

Simultaneous determination of the lactone and carboxylate forms of the camptothecin derivative CPT-11 and its metabolite SN-38 in plasma by high-performance liquid chromatography.

CPT-11 (irinotecan) and mainly its metabolite SN-38 are potent antitumor derivatives of camptothecin. As the active lactone forms of both CPT-11 and SN-38 exist in pH-dependent equilibrium with their respective less potent open-ring hydroxy acid species, the simultaneous monitoring of both forms of both compounds is relevant. CPT-11 and SN-38 derivatives have quite different fluorescence responses.

Optimal sampling strategies for bayesian estimation of docetaxel (Taxotere) clearance.

Docetaxel activity has been documented in many solid tumors, including metastatic breast cancer and non-small cell lung cancer. However, as clinical studies in other tumor types are now being conducted, the validation of an optimal sampling strategy would allow the performance of pharmacokinetics/pharmacodynamics studies with minimum inconvenience for the patient. Six optimal sampling strategies with one to six sampling times were computed, based on the D-optimality theory, using population pharmacokinetic parameters estimated from a large pharmacokinetic database of 547 patients treated in previous Phase II studies.

Simultaneous high-performance liquid chromatographic determination of quinupristin, dalfopristin and their main metabolites in human plasma.

Quinupristin-dalfopristin (30:70, w/w) is a new streptogramin, which has been developed for intravenous use. A specific and sensitive HPLC method was developed to measure simultaneously quinupristin (RP 57669) and dalfopristin (RP 54476) and their main metabolites in human plasma. The metabolites measured by this method were RP 69012 (glutathione-conjugated) and RPR 100391 (cysteine-conjugated) from quinupristin and RP 12536 (natural pristinamycin IIA), from dalfopristin.

Single- and multiple-dose pharmacokinetics of riluzole in white subjects.

Riluzole is a novel neuroprotective agent that has been developed for the treatment of amyotrophic lateral sclerosis. A series of studies was undertaken to establish its pharmacokinetics on single- and multiple-dose administration in young white male volunteers. The mean absolute oral bioavailability of riluzole (50-mg tablet) was approximately 60%.

Population pharmacokinetics of riluzole in patients with amyotrophic lateral sclerosis.

Objectives: To characterize the population pharmacokinetic of riluzole in patients with amyotrophic lateral sclerosis (ALS).

Methods: One hundred patients with ALS who were participating in a multicenter phase III dose-ranging trial of riluzole were sampled on 179 visits. The sampling strategy (two samples per visit) was varied across patients to define the population kinetic profile (full screen).

The pharmacokinetics of quinupristin/dalfopristin in laboratory animals and in humans.

The pharmacokinetics of quinupristin/dalfopristin have been studied in rats, monkeys and humans following intravenous infusion of radiolabelled and unlabelled drug. In rats and monkeys quinupristin and dalfopristin undergo rapid elimination from the blood and wide tissue distribution. Nevertheless, they do not penetrate the central nervous system or cross the placenta to any significant degree and they do not appear to be subject to significant body retention following cessation of administration.

Pharmacokinetics of sparfloxacin in healthy volunteers and patients: a review.

In Caucasian volunteers and patients plasma sparfloxacin concentrations reached a peak of 1.2-1.5 mg/L between 3 and 6 h after a single 400 mg dose; T1/2 ranged from 16 to 22 h.

A population pharmacokinetic model for docetaxel (Taxotere): model building and validation.

A sparse sampling strategy (3 samples per patient, 521 patients) was implemented in 22 Phase 2 studies of docetaxel (Taxotere) at the first treatment cycle for a prospective population pharmacokinetic evaluation. In addition to the 521 Phase 2 patients, 26 (data rich) patients from Phase I studies were included in the analysis. NONMEM analysis of an index set of 280 patients demonstrated that docetaxel clearance (CL) is related to alpha 1-acid glycoprotein (AAG) level, hepatic function (HEP), age (AGE), and body surface area (BSA).

Docetaxel serum protein binding with high affinity to alpha 1-acid glycoprotein.

The binding of docetaxel to human plasma proteins was studied by ultrafiltration at 37 degrees C and pH 7.4. Docetaxel was extensively (> 98%) plasma protein bound.