Parameter in-vivo

M. B. Reddy, A. L. Stinchcomb, R. H. Guy, and A. L. Bunge. Determining dermal absorption parameters in vivo from tape strip data. Pharm. Res. 19 292-298 (2002). 

Jenner AM, Timbrell JA Effect of acute and repeated exposure to low doses of hydrazine on hepatic microsomal enz)nnes and biochemical parameters in vivo. Arch Toxicol 68 240-245, 1994... 

Metabolic parameters. Constants for metabolism can be determined in vitro with tissue homogenates, microsomal preparations, and liver slices [12,13], Another method for assessing metabolic parameters in vivo... 

Similar to the techniques used for calculation of chemical disposition parameters, in vivo biotransformation kinetic parameters of a substrate can be estimated from in vitro systems such as microsomes, freshly isolated hepatocytes, fiver slices, and isolated perfused livers (24). Intrinsic clearance or Michaelis-Menten parameters for the whole liver can also be obtained by scaling in vitro parameters based on the cytochrome P450 enzyme content (25-27). These parameters can also be estimated from in vitro data obtained from recombinant human CYP systems, and also through allometric scaling of clearance estimates from animal PBPK models. 

Mitsukawa K, Yamamoto R, Ofner S et al (2005) A selective metabotropic glutamate receptor 7 agonist activation of receptor signaling via an allosteric site modulates stress parameters in vivo. Proc Natl Acad Sci USA 102 18712-18717... 

AUkhan A, Farahmand S, Maibach HI. Correlating percutaneous absorption with physicochemical parameters in vivo in man agricultural, steroid, and other organic com- poimds. J Appl Toxicol. 2009 29 590-6. 

Thorough photophysical FCS analyses have been carried out on various fluorescent proteins so far EGFP, YFPs, DsRed. These studies produced valuable information for fluorophore usage as fusion partners and successive data evaluation. They also document which photophysical parameters of reporter molecules ought to be determined in vitro to reduce the number of unknown parameters in vivo. We briefly outline these fluorophore studies and continue to hint to impUed options and limitations. 

An understanding of the wear of composite restorative materials requires in vitro testing that measures chemical as well as mechanical parameters. In vivo clinical testing that uses well-chosen clinical criteria also can be useful in studying wear. 

Care should be exercised when attempting to interpret in vivo pharmacological data in terms of specific chemical—biological interactions for a series of asymmetric compounds, particularly when this interaction is the only parameter considered in the analysis (10). It is important to recognize that the observed difference in activity between optical antipodes is not simply a result of the association of the compound with an enzyme or receptor target. Enantiomers differ in absorption rates across membranes, especially where active transport mechanisms are involved (11). They bind with different affinities to plasma proteins (12) and undergo alternative metaboHc and detoxification processes (13). This ultimately leads to one enantiomer being more available to produce a therapeutic effect. 

Since in vivo tests in exposed human populations would involve concomitant exposure to other toxicants, it would be difficult to assess the genotoxic potential of methyl parathion alone. Therefore, additional well-designed in vitro studies using human cell lines are needed to determine the effects of methyl parathion on various genotoxic parameters (e.g., sister chromatid exchange, chromosomal aberrations, unscheduled DNA synthesis). 

Kitchin KT, Brown JL, Kulkami AP. 1992. Predictive assay for rodent carcinogenicity using in vivo biochemical parameters Operational characteristics and complementarity. Mutat Res 266 253-272. 

Liposomes are members of a family of vesicular structures which can vary widely in their physicochemical properties. Basically, a liposome is built of one or more lipid bilayers surrounding an aqueous core. The backbone of the bilayer consists of phospholipids the major phospholipid is usually phosphatidylcholine (PC), a neutral lipid. Size, number of bilayers, bilayer charge, and bilayer rigidity are critical parameters controlling the fate of liposomes in vitro and in vivo. Dependent on the preparation procedure unilamellar or multilamellar vesicles can be produced. The diameter of these vesicles can range from 25 nm up to 50 ym—a 2000-fold size difference. 

The behavior of liposomes in vivo can be influenced to a considerable extent by varying chemical composition and physical properties. Parameters affecting rate of clearance from the blood and tissue distribution include size, composition, dose, and surface characteristics (e.g., charge, hydrophobicity, presence of homing devices such as antibodies). 

The conditions for production of TTX and STX by bacteria are unknown. The low levels of TTX and STX observed in laboratory cultures may indicate that the host environment has not been duplicated. Likely, the composition of culture medium and other physicochemical parameters for TTX and STX production have not yet been defined in vitro. Conversely, bacteria may actually produce only small amounts of TTX and STX in vivo that accumulate in host tissues over long time intervals. 

Data from both in vivo and in vitro systems showed PbTx-3 to have an intermediate extraction ratio, indicating in vivo clearance of PbTx-3 was equally dependent upon liver blood flow and the activity of toxin-metabolizing enzymes. Studies on the effects of varying flow rates and metabolism on the total body clearance of PbTx-3 are planned. Finally, comparison of in vivo metabolism data to those derived from in vitro metabolism in isolated perfused livers and isolated hepatocytes suggested that in vitro systems accurately reflect in vivo metabolic processes and can be used to predict the toxicokinetic parameters of PbTx-3. 

Winiwarter, S., Bonham, N. M., Ax, F., Hallberg, A., Lennemas, H., Karlen, A. Correlation of human jejunal permeability (in vivo) of drugs with experimentally and theoretically derived parameters. A multivariate data analysis approach. J. Med. Chem. 1998, 41, 4939-4949. 

Calculated molecular descriptors including H-bond parameters were used for QSAR studies on different types of permeabiUty. For example, the new H-bond descriptor characterizing the total H-bond ability of a compound, was successfully appUed to model Caco-2 cell permeability of 17 drugs [30]. A similar study on human jejunal in vivo permeabiUty of 22 structurally diverse compounds is described in Ref. [62]. An exceUent one-parameter correlation of human red ceU basal permeabiUty (BP) was obtained using the H-bond donor strength [63] ... 

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