Dose-effect curves and relative biophasic drug levels: Elucidation of these concepts and the illustration of their use for the determination of bioavailability, rate of absorption, and time course of pharmacological response

AbstractActivated protein C (APC) is a natural anticoagulant serine protease in plasma that down-regulates the coagulation cascade by degrading cofactors Va and VIIIa by limited proteolysis. Recent results have indicated that basic residues of 2 surface loops known as the 39-loop (Lys37-Lys39) and the Ca2+-binding 70-80–loop (Arg74 and Arg75) are critical for the anticoagulant function of APC. Kinetics of factor Va degradation by APC mutants in purified systems have demonstrated that basic residues of these loops are involved in determination of the cleavage specificity of the Arg506 scissile bond on the A2 domain of factor Va. In this study, we characterized the properties of the same exosite mutants of APC with respect to their ability to interact with factor VIIIa. Time course of the factor VIIIa degradation by APC mutants suggested that the same basic residues of APC are also critical for recognition and degradation of factor VIIIa. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) of the factor VIIIa cleavage reactions revealed that these residues are involved in determination of the specificity of both A1 and A2 subunits in factor VIIIa, thus facilitating the cleavages of both Arg336 and Arg562 scissile bonds in the cofactor.

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LC-MS/MS method for the determination of diazolic anthelmintic drug levels from sheep and human plasma for use in pharmacokinetic and bioavailability studies

Studia Universitatis Babeș-Bolyai Chemia ◽

10.24193/subbchem.2021.01.14 ◽

2021 ◽

Vol 66 (1) ◽

pp. 181-194

Author(s):

Lénárd Farczádi ◽

◽

Silvia Imre ◽

Laurian Vlase ◽

◽

...

Keyword(s):

Human Plasma ◽

Drug Levels ◽

Anthelmintic Drug

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In Vitro Evaluation of the Sensitivity of a Hyaluronic Acid PEG Cross-Linked to Bovine Testes Hyaluronidase

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2018.046 ◽

2018 ◽

Vol 6 (1) ◽

pp. 20-24 ◽

Cited By ~ 2

Author(s):

Nicola Zerbinati ◽

Torello Lotti ◽

Damiano Monticelli ◽

Virginia Martina ◽

Giovanna Cipolla ◽

...

Keyword(s):

Hyaluronic Acid ◽

Soft Tissue ◽

Chemical Reaction ◽

Time Course ◽

Soft Tissue Augmentation ◽

Facial Soft Tissue ◽

Microplate Reader ◽

Kinetics Of

Neauvia Intense is biocompatible, injectable hyaluronic acid (HA) filler PEG cross-linked for facial soft-tissue augmentation that provides volume to tissues. The aim of the present study is to evaluate the sensitivity of Neauvia Intense in hyaluronidase from bovine testes in a time-course analysis. The test is based on the colourimetric determination of the N-acetyl – D - glucosamine (NAG) released by the hyaluronidase in standardised conditions. The in vitro conditions involve the treatment of Neauvia Intense with a known concentration of the enzyme (6080U/ml). The NAG content was determined at different times to assess the kinetics of the degradation (1h, 3h, 6h, 24h, 48h, 72h, 120h, and 168h); the Ehrlich’s reagent was used for the colourimetric quantification, by the method described by Reissing and colleagues. The intensity of the violet colour developed after the chemical reaction was proportional to the NAG present in each sample. A microplate reader at 585 nm read the absorbance. The amount of NAG released by the product was proportional to the time of incubation with bovine hyaluronidase, reaching a plateau after 168 hours.

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Reactive Diffusion at the Cylindrical Dissolving of Copper in the Solder Melt

Defect and Diffusion Forum ◽

10.4028/www.scientific.net/ddf.312-315.387 ◽

2011 ◽

Vol 312-315 ◽

pp. 387-392 ◽

Cited By ~ 1

Author(s):

Jaromír Drápala ◽

Alena Struhařová ◽

Daniel Petlák ◽

Vlastimil Vodárek ◽

Petr Kubíček

Keyword(s):

Time Course ◽

Solid Phase ◽

Accurate Determination ◽

Theoretical Description ◽

Reactive Diffusion ◽

Interface Boundary ◽

Boundary Movement ◽

Long Time ◽

Melt Cooling

Problems of reactive diffusion at the solid phase and melt contact were studied theoretically and experimentally. The main intention was to calculate the time course of the solid phase dissolving in the case of cylindrical dissolving. These calculations were carried out on the assumption for the rate constant of dissolving K = const. In our work we give heed especially to the dominating process, which is the solid metal A dissolved in the melt B. During the dissolving the melt B saturates with the metal A and the process is influenced by convections which are characteristic for the given experimental configuration. A theoretical description of the kinetics of the solid phase dissolving in the melt will be presented for the case of cylindrical dissolving. The aim is to derive a relation for the interface boundary movement c(t) in dependence on time and a time course of growth of the element A concentration in the melt B. There are problems with accurate determination of the interface boundary movement after certain heating times of specimens, when it is observed experimentally, since intermetallic phases create in the original A metal at both the diffusion and cooling and some phases segregate at the solidifying melt cooling. The main intention was an experimental study of the copper dissolving in the tin melt. Experiments aimed to the determination of the Cu wires (diameters from 0.5 to 3.5 mm) dissolution in the solder melt were carried out at various selected temperatures and times. Rapid growth of phases in the metal A and determination of the thickness of layers with these phases pose considerable time demands to X-ray micro-analyses (WDX, EDX) of specimens after their long-time heating.

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DOSE REGIMENS OF HUMAN GROWTH HORMONE: EFFECTS OF CONTINUOUS INFUSION AND OF A GELATIN VEHICLE ON GROWTH IN RATS AND RATE OF ABSORPTION IN RABBITS

Journal of Endocrinology ◽

10.1677/joe.0.0870303 ◽

1980 ◽

Vol 87 (2) ◽

pp. 303-312 ◽

Cited By ~ 17

Author(s):

P. MARY COTES ◽

W. A. BARTLETT ◽

ROSE E. GAINES DAS ◽

P. FLECKNELL ◽

R. TERMEER

Keyword(s):

Growth Hormone ◽

Human Growth Hormone ◽

Plasma Levels ◽

Time Course ◽

Human Growth ◽

Daily Injection ◽

Glycine Buffer ◽

Hormone Effects ◽

Rate Of Absorption ◽

Hypophysectomized Rats

Different methods for administration of human growth hormone (hGH) have been examined with a view to efficient use of the limited amounts of hGH at present available for clinical use. We found that in hypophysectomized rats (1) hGH administered by continuous subcutaneous infusion induced a greater increase in body weight (referred to throughout as growth) than hGH administered by intermittent (daily) injection and (2) intermittent injections of hGH dissolved in 16% gelatin induced more growth than hGH dissolved in a glycine buffer. It was further found that (1) hGH dissolved in 16% gelatin compared with hGH dissolved in a glycine buffer induced lower maximal levels of immunoreactive plasma hGH and between 7 and 9 h after treatment higher plasma levels when injected subcutaneously in rabbits, (2) 125I-labelled hGH added as a tracer to hGH in gelatin was removed more slowly from subcutaneous injection sites in rabbits than 125I-labelled hGH given with hGH in glycine buffer and (3) changes in the ratio of hGH to gelatin had little effect on the time-course of plasma levels of hGH in the rabbit. Addition of the protease inhibitors aprotinin or 6-aminohexanoic acid, to injection of hGH in gelatin or glycine did not induce any consistent increase in plasma levels of hGH.

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