Drug studies

S. Ramcharan, R. A. PeUegtin, R. M. Ray, and co-workers. The Walnut Creek Contraceptive Drug Study A Prospective Study of the Side Effects of Oral Contracptives, Vol. 3, U.S. Dept, of Health and Human Services, Government Printing Office, 1981. 

Drug Study N Dose Time from Symptom Onset (h) Result Symptomatic ICH (Treatment vs. Placebo)... 

IMPLICATIONS OF NEUROTRANSMITTER MALFUNCTION FROM DRUG STUDIES... 

In contrast, iproniazid, introduced in 1951 for treatment of tuberculosis, induced euphoria and was described as a psychic energiser . In fact, these patients, when given iproniazid, could become quite disruptive and this action was regarded as an undesirable side-effect However, its beneficial effects in depression were soon recognised and it was regarded as the first effective antidepressant drug. Studies of peripheral sympathetic neurons, later extended to noradrenergic neurons in the brain, showed that iproniazid irreversibly inhibits the catalytic enzyme, monoamine oxidase (MAO). Because only cytoplasmic monoamines are accessible to MAO, inhibition of this enzyme first increases the concentration of the pool of soluble transmitter but this leads to a secondary increase in the stores of vesicle-bound transmitter i.e. the pool available for impulse-evoked release (Fillenz and Stanford 1981). 

Conners, C.K. A teacher rating scale for use in drug studies with children. Am J Psychiatry 126 152-156, 1969. 

Hard gelatin capsules are uniquely suitable for blinded clinical tests and are widely used in preliminary drug studies. Bioequivalence studies of tablet formulations may be conveniently blinded by inserting tablets into opaque capsules, often along with an inert filler powder. Even capsule products may be disguised by inserting them into larger capsules. 

R. G. Hollenbeck and P. P. Lamy, Dosage form considerations in clinical trials involving elderly patients, in Drug Studies in the Elderly Methodological Concerns (N. R. Cutler and P. K. Narang, eds.), Plenum Publishing, New York, 1986, pp. 335-353. 

Drug Studies in Pediatric Patients Medical Officer s Review Statistical Review Evaluation Chemistry, Manufacturing and Controls CDER Labeling and Nomenclature Committee Clinical Pharmacology/Biopharmaceutics Microbiologist s Review Pharmacokinetics Review Carcinogenicity Assessment... 

Where the drug studied is a racemate, the pharmacokinetics, including potential interconversion, of the individual enantiomers should be investigated in Phase I clinical studies. Phase I or II data in the target population should indicate whether an achiral assay, or monitoring of only one optical isomer where a fixed ratio is confirmed, will be adequate for pharmacokinetic evaluation. If the racemate has already been marketed and the sponsor wishes to develop the single enantiomer, additional studies should include determination of any conversion to the other isomer and whether there is any difference in pharmacokinetics between the single enantiomer administered alone or as part of the racemate. 

Drug studies demonstrated a requirement that most proteins destined for fast axonal transport traverse the Golgi stacks, where membrane proteins are post-transla-tionally modified, sorted and packaged [9] (Fig. 28-7). This suggests that proteins in fast axonal transport must either pass through the Golgi complex or associate with... 

FIGURE 1.17 Load-wash-elution profile of SPE extracts of d-enantiomer of atraizole drug studied on a 384 well plate.119 (Reproduced with permission from the American Chemical Society.)... 

Hart, C. (1999). Getting past the politics and paperwork of pediatric drug studies. Modern Drug Discovery 2 15-16. 

A double-blind control is also an essential element of drug studies. Double-blind means that neither experimenter nor subject knows who is receiving the active treatment or the placebo. Again, this is to eliminate potential bias from both parties. Otherwise, experimenters could unwittingly influence the outcome of the study by subtly treating subjects differently. 

Herbal drugs can have general or specific effects on cognition. To understand the results of neuropsychological testing in drug studies, it will be useful to briefly discuss the breakdown of cognitive functions. 

Media critics were predictably more interested in drug studies done in a military setting than those conducted within the hallowed halls of academe. Their reporting would have been less biased if they had noted that we never gave more (and usually much less) than 300 meg of LSD to any of our volunteers. The problem, of course, was that Edgewood kept reporters in the dark by classifying most of our work, thus keeping it out of the public s purview. 

The following paragraphs sum up the welter of control mechanisms that ultimately governed drug studies at Edgewood (as well as throughout the entire Army). 

This is a fair summary of the attractions offered to would-be volunteers. (Civilian investigators also frequently provide generous financial inducements to attract volunteers for their drug studies.) But our volunteers did not receive any additional privileges or compensation for participating in two or more different experiments. Subjects who had already experienced the delirium produced by BZ were often willing (or even offered) to repeat the experience two weeks later. Asked to put a price on a second consent, one man said 25. This willingness can hardly be attributed to the previously mentioned inducements, since they were already earned. 

But it is not the last page of the story. I have relegated the details of the science part of my drug research to the appendix. There you will find a more detailed technical account of the studies described in earlier chapters. Some of the specifics of our drug studies have never been publicly disseminated and if you are scientifically inclined, you will want to read the details. Up to now, this book has been a subjective presentation of my own experiences and opinions. The appendix, however, is a more impersonal compilation of what we learned -information that should be made available to the research community. Viewed dispassionately, it is certainly of greater importance than my personal story. But as you have probably judged by now, I usually have more fun talking about myself ... 

We also wanted to add some way to assess time estimation ability, often included in drug studies. Most previous investigators required the individual to estimate when an arbitrary time interval had elapsed, or to produce a specific time interval, such as one minute. Although popular, we thought these tasks were too imprecise for our purposes. It was often simply a one-trial test, given without prior practice, and useful mainly as a diagnostic tool for psychiatrists and neurologists. 

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