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Imax Value (imax + value)

Distribution by Scientific Domains

Chemistry	75%

Selected Abstracts

Pharmacodynamic interaction of recombinant human interleukin-10 and prednisolone using in vitro whole blood lymphocyte proliferation

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2002
Abhijit Chakraborty
Abstract Prednisolone, a commonly used synthetic corticosteroid, and IL-10, a cytokine under investigation for strong antiinflammatory properties, are being contemplated as a potential joint therapeutic regimen in immune disorders. Their pharmacodynamic interactions were examined in blood from healthy adult male and female volunteers using an in vitro phytohemagglutinin (PHA)-stimulated whole,blood lymphocyte proliferation technique. Isobolograms along with parametric competitive and noncompetitive interaction models were used to determine the nature and intensity of interactions. Single drug effects show prednisolone more efficacious in inhibiting lymphocyte proliferation with an IC50 of 3.3 ng/mL and Imax value of 1, signifying complete suppression. Analogous parameters for IL-10 were 16.2 ng/mL for IC50 and 0.89 for Imax. There were no significant differences in the single drug immunosuppressive effects among genders. Their joint effects showed additive interaction based on isobolographic analysis. Parametric analysis using the competitive interaction model described their interaction as slightly synergistic, while the noncompetitive interaction modeling indicate a small degree of antagonism. Also, the joint effects in females tend to be more antagonistic than males. Concomitant use of prednisolone and IL-10 should thus reflect the net additive responses to concentrations of each agent. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1334,1342, 2002 [source]

Energy-resolved in-source collisionally induced dissociation for the evaluation of the relative stability of noncovalent complexes in the gas phase

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 23 2005
Nataliya Lyapchenko
Energy-resolved in-source collisionally induced dissociation (CID) studies on the complexation of alkali metal cations by some crown ethers, nucleic acid bases, and amino acids have been performed. It has been shown that the cone voltage corresponding to the maximum ion abundance (Vc,Imax) of the breakdown curve is characteristic of a given ion and not influenced by the cone desolvation process or the composition of the solution. Very good agreement of the Vc,Imax value with the bond strength of the ion has been observed. Determination of the Vc,Imax values for different ionic species is a useful, simple, and inexpensive way to obtain their relative stabilities in in-source CID conditions. Copyright © 2005 John Wiley & Sons, Ltd. [source]

The prediction of human response to ONO-4641, a sphingosine 1-phosphate receptor modulator, from preclinical data based on pharmacokinetic,pharmacodynamic modeling

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 7 2010
Tomoya Ohno
Abstract The pharmacokinetic (PK) and pharmacodynamic (PD) parameters of ONO-4641 in humans were estimated using preclinical data in order to provide essential information to better design future clinical studies. The characterization of PK/PD was measured in terms of decreased lymphocyte counts in blood after administration of ONO-4641, a sphingosine 1-phosphate receptor modulator. Using a two-compartment model, human PK parameters were estimated from preclinical PK data of cynomolgus monkey and in vitro human metabolism data. To estimate human PD parameters, the relationship between lymphocyte counts and plasma concentrations of ONO-4641 in cynomolgus monkeys was determined. The relationship between lymphocyte counts and plasma concentrations of ONO-4641 was described by an indirect-response model. The indirect-response model had an Imax value of 0.828 and an IC50 value of 1.29,ng/ml based on the cynomolgus monkey data. These parameters were used to represent human PD parameters for the simulation of lymphocyte counts. Other human PD parameters such as input and output rate constants for lymphocytes were obtained from the literature. Based on these estimated human PK and PD parameters, human lymphocyte counts after administration of ONO-4641 were simulated. In conclusion, the simulation of human lymphocyte counts based on preclinical data led to the acquisition of useful information for designing future clinical studies. Copyright © 2010 John Wiley & Sons, Ltd. [source]