Human volunteer studies, data

In vivo Studies in Animals 325 Studies in Human Volunteers 326 DATA ANALYSIS CHALLENGES 326 Incomplete Recovery 327... 

Thus, despite the value of human volunteer studies, the technical and ethical constraints for studying dermal absorption of pesticides in human volunteers prevail. As a consequence, only limited data on the dermal absorption of chemicals are available from human volunteer studies. This is in contrast to pharmaceutical products, where the use of human volunteers is considered to be the only relevant approach to generate data of precise relevance to man. 

Grafitt SJ, Jones K, Mason HJ, and Cocker J (2002) Exposure to the organophosphate diazinon Data from a human volunteer study with oral and dermal doses. Toxicology Letters 134(1-3) 105-113. 

The basis of the CTX scheme is that, together with a detailed clinical trial protocol, summaries of chemical, pharmaceutical, pharmacological, pharmacokinetic, toxicological and human volunteer studies may be permitted instead of the additional details normally required for a CTC or product license application. This CTX scheme is based on the requirement that (a) a doctor must certify the accuracy of the data (b) the supplier undertakes to inform the Licensing Authority of any refusal to permit the trial by an ethical committee and (c) the supplier also undertakes to inform the Licensing Authority of any data or reports concerning the safety of the product. 

There are clear ethical constraints that prevent human research that could definitively answer the questions of concern regarding the military operational and civilian health risks of exposure to low-levels of chemical warfare nerve agents. Only three sources of relevant human data are available for analysis. These data are from either past human volunteer studies, reports based on accidental exposures, or reports of the consequences of malicious releases of the agents. While these sources are valuable, the data have some limitations for deriving dose-response relationships because of inferior analytical and clinical methods or the lack of precise estimates of exposure. 

Dermal Absorption and Dermal Dose-Resnonse. These data are needed in the risk assessment of field workers, mixers/loaders, applicators, and flaggers they may also be used in the development of reentry intervale. The data gathered informs CDFA of how much of the chemical actually enters the body once it comes into contact with the skin. Guides for these types of studies in test animals are available through, and were conducted by, the CDFA. At times, data from human volunteer studies are available when available, this type of information usually takes precedence over animal test data. 

S. J. Garfitt, K. Jones, H. J. Mason and J. Cocker, Development of a urinary biomarker for exposure to the organophosphate propetamphos data from an oral and dermal human volunteer study. Biomarkers, 2002, 7, 113-122. 

This will extend, and partially replace, the traditional approach to biomedical research that is based on studying living cells or tissues in vitro, or on obtaining data from human volunteers in vivo, by introducing in silico experiments (a term, derived from the currently prevaihng sihcon-based computer chips). 

Studies on workers in an occupational setting showed a dose-response relationship between the concentration of acrylonitrile of inspired air and the recovery of metabolites in the urine (Houthuijs et al. 1982 Sakurai et al. 1978). In a controlled study using human volunteers, urinary metabolite data suggested that the elimination of acrylonitrile followed first-order kinetics, with a half- life of seven to eight hours (Jakubowski et al. 1987). 

The effects of antibiotics on anaerobic and aerobic flora are shown in table 3. These data are from a variety of studies of human volunteers or patients given preoperative antibiotics but receiving various antibiotics by various routes [31-44], Variations in data can be explained by methodological differences between studies as well as... 

In a study designed to gather pharmacokinetic data, two healthy human volunteers were exposed to HFC-134a at 4,000 ppm delivered via a mouthpiece (Vinegar et al. 1997). The exposures were scheduled to last for 30 min. Blood samples were collected throughout the exposures. The exposures were abruptly terminated following an unexpected and uncontrollable rise in pulse rate in one subject and a drop in pulse rate and blood pressure and loss of consciousness in the second. This vasovagal response is sometimes observed... 

Typically, BA and BE are assessed by cumbersome and expensive studies in human volunteers. But, under certain circumstances, regulatory agencies may waive the requirement for the submission of evidence measuring the in vivo BA or establishing BE. This is referred to as a biowaiver . The application of a biowaiver requires that supportive in vitro dissolution data are meaningful in terms of in vivo performance of the drug product. 

Human clinical studies Plasma levels of hyperforin were followed for 24 hours in two studies with healthy volunteers after administration of film-coated tablets containing 300 mg SJW extract representing 14.8 mg hyperforin (Table 2) (72). In the first crossover study, six male volunteers received 300, 600, or 1200 mg of a SJW extract preparation (WS 5572, Dr. Willmar Schwabe Arzneimittel, Karlsruhe, Germany) after a 10-hour fasting time. Maximum plasma levels of 150 ng/mL (approximately 280 nM) were reached after 3.5 hours after intake of 300 mg SJW extract. Half-life and MRT were 9 and 12 hours, respectively. Hyperforin pharmacokinetics were linear up to 600 mg of the extract. Increasing the doses to 900 or 1200 mg resulted in lower Cmax and AUC values than those expected from linear extrapolation of data from lower doses. In a repeated dose study with seven healthy volunteers, no accumulation of hyperforin in plasma was observed after intake of 900mg/day SJW extract for seven days. The estimated steady-state plasma concentrations of hyperforin after intake of 3 x 300mg/day was approximately 100 ng/mL (approximately 180 nM) (Table 2) (72). 

Wall et al.9 administered 1.3 pg/kg of 3H-PCP intravenously to human volunteers and collected blood samples for 72 h. Data from this study suggested a two-compartment pharmacokinetic model with a plasma half-life for PCP of 7 to 16 h. Domino et al.10 further analyzed the data from Wall et al. and developed a more complex three-compartment PK model. The reported half-lives for... 

At the very least, to support limited topical exposure, for example, single application patch test in the human, genotoxicity data are required (and a favourable judgement on the sensitization and corrosive potential of the material). The following types of study may be performed using human volunteers. 

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