Human experimentation

For dmgs approved originally between 1938 and 1962, the FDA has utilized the Abbreviated New Dmg AppHcation (ANDA) for review of generic products that are pharmaceutical equivalents of the initially approved products. In this way, costiy dupHcation of animal and human experimentation is avoided. The new manufacturer has to show only that its manufacturing methodology, specifications, quaUty control, and labeling are acceptable. In some cases, the FDA does require proof of bioequivalence. 

Gouzoulis- Mayfrank E, Hermle L, Thelen B et al (1998) History, rationale and potential human experimental hallucinogenic drug research in psychiatry. Pharmacopsychiatry (Suppl)31 63-68... 

Humphreys TL, Baldridge LA, Billings SD, Campbell JJ, Spinola SM. Trafficking pathways and characterization of CD4 and CD8 cells recruited to the skin of humans experimentally infected with Haemophilus ducreyi. Infect Immun 2005 73 3896-902. 

Coupling with its intravenous pharmacokinetic parameters, the extended CAT model was used to predict the observed plasma concentration-time profiles of cefatrizine at doses of 250, 500, and 1000 mg. The human experimental data from Pfeffer et al. [82] were used for comparison. The predicted peak plasma concentrations and peak times were 4.3, 7.9, and 9.3 qg/mL at 1.6, 1.8, and 2.0 hr, in agreement with the experimental mean peak plasma concentrations of... 

Russell WMS, Burch RL (1959) The principles of humane experimental technique. Methuen Co. Ltd., London, (Revised 1992, Universities Federation for Animal Welfare, Herts, England.) http //altweb.jhsph.edu/publications/humane exp/het-toc.htm... 

S Legramante, J.M. et al. (2009) Cardiac autonomic regulation after lung exposure to carbon nanotubes. Human Experimental Toxicology, 28 (6-7), 369-375. 

Cabal J., Kassa J., Severa J. A comparison of the decontamination efficacy of foammaking blends based on cationic and nonionic tensides against organophosphorus compounds determined in vitro and in vivo. Human Experimental Toxicology 22, 507-514(2003). 

West, L.J. Defining critical windows in the development of the human immune system, Human Experimental Toxicology 21, 499,2002. 

Koeter, H. International harmonization of immunotoxicity testing. Human Experimental Toxicology, 14(1), 151-154, 1995. 

No modern studies of the human pharmacokinetics of LSD have been done, largely because human experimentation has virtually stopped. An older study that used a spectrofluorometric technique for measuring plasma concentrations of LSD was done in humans given doses of 2 Mg/kg i.v. After equilibration had occurred in about 30 min, the plasma level was between 6 and 7 ng/ml. Subsequently, plasma levels gradually fell until only a small amount of LSD was present after 8 hr. The half-life of the drug in humans was calculated to be 175 min (2). Subsequent pharmacokinetic analysis of these data indicated that plasma concentrations of LSD were explained by a two-compartment open model. Performance scores were highly correlated with concentration in the tissue (outer) compartment, which was calculated at 11.5% of body weight. The new estimation of half-life for loss of LSD from plasma, based on this model, was 103 min (47). 

Clode SA, Riley RA, Blowers SD, et al. 1991. Studies on the mutagenicity of a zinc oxide-hexachloroethane smoke. Human Experimental Toxicology 10 49-57. 

Some degree of standardization of methodologies for rats and human experimentation must be done before a reasonable comparison can be made on the correlation between the calcium absorption responses of these two species. 

Cognitive effects Animais Cognitive effects of nicotine have been observed in several species, including humans. Experimental studies have focused primarily on the effects on attention and memory. Cognitive benefits are seen after both acute and chronic administration (Levin et al. 1992). In experimental animals, nicotine improves learning and memory on a variety of tasks. Conversely, the nicotinic antagonist mecamylamine... 

Dick D, Sauder DN, Chu 1. 1995. In vitro and in vivo percutaneous absorption of 14C-chloroform in humans. Human Experimental Toxicology 14 260-265. 

Safety, ethical, and legal considerations require that the utmost care be exercised in human experimentation. The risk inherent in this work can be minimized by the proper design of facilities for human exposure to reactive gases, such as ozone and sulfur dioxide, and reactive gas mixtures. Standards for the exposure of humans to such controlled atmospheres should be discussed by national groups and agencies, such as the American Medical Association and the National Institutes of Health. 

More recently, Merz et have studied the circulating lymphocytes of humans experimentally exposed to ozone at 0.5 ppm for 6-10 h. A statistically significant increase in the number of minor chromosomal abnormalities (not breaks) was observed it reached a peak about 2 weeks after exposure and later returned to normal. This delay in the development of chromosomal abnormalities observed after ozone exposure in both hamsters and humans differs from that observed in human radiation studies, in which aberrations tend to remain roughly constant over 3-4 weeks. This raises the possibility that the ozone-induced abnormality is related to a postreplication repair process. 

One study of humans experimentally exposed to ozone showed transient development of minor chromosomal abnormalities in circulating lymphoc es. 

In human experimental studies, variables to be considered and controlled include pollutant gas concentration, humidity, temperature, light intensity, noise, particles, and the presence of other gases. 

In interpreting the results of human experimental studies with pure ozone in relation to the oxidant standard, it must be remembered that the other oxidants ordinarily present in smog were absent. Conceivably, a larger difference may be necessary between the lowest concentration of pure ozone at which an observed effect occurred and the air quality standard than between the lowest concentration of oxidant mixtures and the standard. 

It is apparent that controlled human experimental studies are needed, but are cumbersome and costly. Other limitations include restrictions as to the number of measurable responses and the fact that individual pollutants are usually studied, rather than ambient mixtures. In addition, healthy subjects are usually studied, rather than sensitive population groups. The results of these studies are applicable to acute effects but their relation, if any, to chronic effects is not known. 

Safety, ethical, and legal considerations require that the utmost care be exercised in human experimentation. The risk inherent in this work can be minimized by taking reasonable precautions while ensuring the satisfactory performance of the study. 

Nyvad B and Fejerskov O (1990) An ultrastructural study of bacterial invasion and tissue breakdown in human experimental root-surface caries. J Dent Res 69, 1118-1125. 

Fisher RL, Hasal SJ, Sipes IG, et al. 1995. Comparataive metabolism and toxicity of dichlorobenzenes in Sprague-Dawley, Fischer-344 and human liver slices. Human Experimental Toxicology 14 414-421. 

In 1959, a book titled The Principles of Humane Experimental Technique was published, which introduced the concept of the 3Rs (Russell and Burch 1959). The 3Rs stand for reduction, refinement, and replacement. 

Russell, W. M. S. and Burch, R. L. 1959. The Principles of Humane Experimental Technique. London Methuen, http //altweb.jhsph.edu/publications/humane exp/foreward.htm SIS. 2007. Division of Specialized Information Services, National Library of Medicine http //www.nlm.nih. gov/pubs/factsheets/sis.html... 

Russell WMS, Burch RL. The Principles of Humane Experimental Technique. London Methuen and Co Ltd, 1959. 

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