Phamacokinetics

PURPOSE: The goals in this study were several-fold. First, to optimize the in vivo phage display methodology by incorporating phage pharmacokinetic properties, to isolate peptides that target the brain microvasculature, and then to build focused libraries to obtain structure activity relationship information in vivo to identify the optimal targeting motif. MATERIALS AND METHODS: The blood pharmacokinetics of filamentous and T7 phage were evaluated to choose the optimal platform...

OBJECTIVE: To study the phamacokinetics and relative bioavailability of combination Radix Angelicae Sinensis and Cortex Cinnamomi. METHOD: The content of ferulic acid in plasma was determined directly by HPLC after oral administration of Cortex Cinnamomi in combination individually with Radix Angelicae Sinensis. The plasma concentration-time curve were plotted. The main pharmacokinetic parameters and relative bioavailability were obtained. RESULT: The plasma concentration-time curve of fenalic aclid conformed to one-compartment model...

To facilitate the assessment of drug safety and determination of phamacokinetics, an anion exchange isolation of zidovudine triphosphate (ZDV-TP) from human peripheral blood mononuclear cells (hPBMC), coupled with dephosphorylation, desaltation, and detection by liquid chromatography-tandem mass spectroscopy (LC-MS-MS) was validated. hPBMCs were harvested from whole blood, lysed, and a suspension of intracellular ZDV-TP was produced. ZDV-TP was isolated from ZDV, ZDV-monophosphate (ZDV-MP), and ZDV-diphosphate (ZDV-DP), which were all present in the cell lysate, by performing a salt gradient anion exchange SPE...

Degarelix (FE200486, Ac-d-2Nal(1)-d-4Cpa(2)-d-3Pal(3)-Ser(4)-4Aph(l-Hor)(5)-d-4Aph(Cbm)(6)-Leu(7)-ILys(8)-Pro(9)-d-Ala(10)-NH(2)) is a potent and very long acting antagonist of gonadotropin-releasing hormone (GnRH) after subcutaneous administration in mammals including humans. Analogues of degarelix were synthesized, characterized, and screened for the antagonism of GnRH-induced response in a reporter gene assay in HEK-293 cells expressing the human GnRH receptor. The duration of action was also determined in the castrated male rat assay to measure the extent (efficacy and duration of action) of inhibition of luteinizing hormone (LH) release...

Huperzine-A (Hup-A), a biologically potent, reversible acetylcholinesterase inhibitor for the treatment of Alzheimer disease (AD) in China, has very low blood concentration. In order to study the pharmacokinetics of newly developed Hup-A transdermal patches in animal, a rapid and sensitive ion-pair reverse-phase high performance liquid chromatography (RP-HPLC) method for the determination of Hup-A in beagle dog serum using mebendazole as internal standard has been developed and validated. The analyte and internal standard were extracted from serum using chloroform-isopropanol (95:5, v/v), analyzed on a C (18) column (5 microm, 150 mm x 4...

OBJECTIVE: To study the phamacokinetics and targeting characteristics of adriamyin in dogs following embolization of hepatic artery with adriamyin-lipiodol emulsion (AD-E). METHODS: After injection of adriamycin solution and the emulsion, respectively, into the hepatic artery via a femoral artery of the dogs, the concentration of adriamycin in the peripheral venous blood and hepatic tissue were determined by high-performance liquid chromatography. RESULTS: The concentration of adriamycin in peripheral venous blood was significantly lowered after AD-E embolization in comparison with that after adriamycin solution injection...

Resveratrol, trans-3,5,4'-trihydroxystilbene, was first isolated in 1940 as a constituent of the roots of white hellebore (Veratrum grandiflorum O. Loes), but has since been found in various plants, including grapes, berries and peanuts. Besides cardioprotective effects, resveratrol exhibits anticancer properties, as suggested by its ability to suppress proliferation of a wide variety of tumor cells, including lymphoid and myeloid cancers; multiple myeloma; cancers of the breast, prostate, stomach, colon, pancreas, and thyroid; melanoma; head and neck squamous cell carcinoma; ovarian carcinoma; and cervical carcinoma...

A woman, thyroidectomised because of a thyroid papillary carcinoma, interrupted temporarily her levothyroxine intake in order to be subjected to an extension study five weeks later. To minimise her symptoms for the first three weeks, a treatment was prescribed consisting of one 25 micro g-capsule of triiodothyronine every 8 hours. Nine days later she complained of abdominal pain, nausea, vomiting, fever of 40 degrees C and chest discomfort. A serum total triiodothyronine of 575.2 nmol/l was measured by chemoluminiscent immunoassay eleven hours after the intake of the latest capsule (normal level: 1...

OBJECTIVE: To investigate the phamacokinetics and serum bactericidal activities (SBAs) of trovafloxacin, cefepime and amikacin alone and trovafloxacin in combination with cefepime or amikacin, so that the most favorable combination with trovafloxacin can be determined. METHODS: In this open, randomized, crossover study, 12 healthy volunteers (six females, six males; mean age +/- SD, 25.1 +/- 2.6 years) received an infusion of either 300 mg of alatrovafloxacin or 2000 mg of cefepime or 6 mg/kg body weight amikacin alone, or 300 mg of alatrovafloxacin plus 2000 mg of cefepime or plus 6 mg/kg body weight amikacin...

We describe a new method for selective cell targeting based on the use of light-absorbing microparticles and nanoparticles that are heated by short laser pulses to create highly localized cell damage. The method is closely related to chromophore-assisted laser inactivation and photodynamic therapy, but is driven solely by light absorption, without the need for photochemical intermediates (particularly singlet oxygen). The mechanism of light-particle interaction was investigated by nanosecond time-resolved microscopy and by thermal modeling...

Phamacokinetics is proposed to study the absorption, the distribution, the biotransformations and the elimination of drugs in man and animals. A single kinetic profile may be well summarized by Cmax, Tmax, t 1/2 and AUC and, having more than one profile, 8 parameters at least, the mean and standard deviation of these parameters, may well summarize the drug kinetics in the whole population. A more carefull description of the data can be obtained interpolating and extrapolating the drug concentrations with some mathematical functions...

AIM: A single-chain antibody fragment, ND-1scFv, against human colorectal carcinoma was constructed and expressed in E.coli, and its biodistribution and pharmacokinetic properties were studied in mice bearing tumor. METHODS: V(H) and V(L) genes were amplified from hybridoma cell IC-2, secreting monoclonal antibody ND-1, by RT-PCR, and connected by linker (Gly(4)Ser) (3) to form scFv gene, which was cloned into expression vector pET 28a(+) and finally expressed in E...

Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate, MK-217, Fosamax), an aminobisphosphonate, is a potent inhibitor of osteoclast-mediated bone resorption and is used for the treatment of bone disorders, osteoporosis and Pagets disease of bone. Alendronate, like all bisphosphonates, is absorbed poorly in animals and humans; oral bioavailability is less than 2% in all species studied, including humans. Systemically available alendronate disappears very rapidly from plasma, and the drug is either taken up by bone tissues or excreted by the kidneys...

No abstract text is available yet for this article.

Inhalant abuse is a rapidly growing health problem particularly among adolescents. Yet we know little about the neural mechanisms underlying the abuse liability of inhalants, particularly when compared to other addictive drugs. Specifically, our understanding of the relationship between the regional brain phamacokinetics and features classically associated with drug reinforcement is lacking. Under the hypothesis that the abuse liability of toluene can be related to its pharmacokinetic properties and the pattern of regional brain uptake, we developed the methodology for radiolabeling and purifying [11C]toluene for use in PET studies...

The objective of this study was to determine the pharmacokinetic profile of total platinum administered by hyperthermic peritoneal perfusion (HPP) in 16 patients with ovarian cancer. The patients had a performance status of lIIalpha/b/c on the FIGO scale. They received 60, 80 or 100 mg of cisplatin. The percent of cisplatin remaining in the body after the peritoneum was emptied averaged 65% (41.7-85.4%). The average ratio between peritoneal drug concentrations and plasma concentrations was 73. A Bayesian estimation of individual phamacokinetic parameters was carried out using the non-linear mixed-effect modeling approach as implemented in the NONMEM computer program...

BACKGROUND: In-stent restenosis is caused by neointimal hyperplasia. Sirolimus (rapamycin; Wyeth Research, Radnor, Pennsylvania, USA) inhibits vascular smooth muscle cell proliferation and we evaluated the efficacy of sirolimus in reducing neointimal formation in a rabbit iliac model and in-vivo pharmacokinetics in the porcine coronary model. DESIGN: Randomized, blinded, prospective animal study. METHODS: Bilateral rabbit iliac artery stent implantation was performed using crossflex stents (Cordis Corporation, Warren, New Jersey, USA) coated with sirolimus incorporated in a nonerodable polymer...

BACKGROUND: Pleconaril is an orally active, broad spectrum antipicornaviral agent with activity against nonpolio enteroviruses. Pleconaril phamacokinetics was evaluated in 16 neonates (16.4 +/- 8.7 days postnatal age) with suspected enteroviral infection. METHODS: Pleconaril (5 or 7.5 mg/kg) was administered orally to study subjects and plasma pleconaril concentrations quantified from serial blood samples obtained during 24 h after a single oral dose by gas chromatography with electrochemical detection...

The pharmacokinetics of a low molecular weight heparin (LMWH; Fragmin D) was studied in dogs after intravenous and subcutaneous administration, based on antifactor Xa- (anti-fXa-) activity. Each dosage was examined in 5 adult Beagles. After intravenous application of 25, 50 and 100 anti-fXaU./kg body weight (BW) the mean peak plasma heparin activity of 0.52 +/- 0.12 (x +/- s), 1.08 +/- 0.23 and 1.86 +/- 0.17 anti-fXaU./ml, respectively, was measured. After subcutaneous application of 50, 100 and 200 anti-fXaU...

Pharmacokinetics of a 240 mg single dose of oral dihydroartemisinin (DHA) was investigated in 8 healthy (5 males, 3 females) Vietnamese volunteers. Plasma concentrations were measured by high-performance liquid chromatography with electrochemical detection in the reductive mode. The concentration time profile of DHA was fitted with one-compartment model with a lag time. Pharmacokinetics of DHA is comparable between males and females even when adjusted with dosage. The median (range) values of pooled pharmacokinetics of oral DHA were: t(lag) 0...