Subject tolerance

The degree of study subject tolerability to a drug should be assessed in conjimction with the laboratory safety and efficacy data, so that an overall risk to benefit assessment can be made. Poorly tolerated drugs, however efficacious for use in self-limiting non-serious diseases, are unlikely to become successful medicines. On the other hand, study subjects with serious illnesses, such as active rheumatoid arthritis, are frequently quite prepared to put up with poorly tolerated drugs (e.g. intramuscular gold injections or intra-articular steroid injections) if efficacy is good and the alternatives are no more attractive. 

Human subjects tolerated 4000 ppm for 6 hours without apparent effect other than slight irritation of the eyes tolerance to higher exposures appears to develop after a single exposure of 1,3-butadiene. Exposure of two human volunteers to 8000 ppm for 8 hours caused eye and upper respiratory tract irritation. ... 

In an experimental investigation, four human subjects tolerated 0.57 ppm iodine vapor for 5 minutes without eye irritation but all experienced eye irritation in 2 minutes at 1.63 ppm. In patients exposed to air saturated with iodine vapor for 3-4 minutes for therapeutic purposes, there was brown staining of the corneal epithelium and subsequent spontaneous loss of the layer of tissue recovery occurred within 2-3 days. Iodine in crystalline form or in strong solutions is a severe skin irritant it is not easily removed from the skin, and the lesions resemble thermal burns with brown... 

Janatu inert Randomized 92 CD subjects Not 11 subjects No serology (refer to Normal villous Most subjects tolerated oats in... 

Janatuinen et al. (2000) ( continuation of Janatuinen et al, 1995) Randomized controlled Same study population Serum from 92 CD subjects 52 in remission 26 oats/26 control 40 new Dx of CD 19 oats/21 control 6 months 12 months Mean 49.9 14.7 g/day Mean 46.6 13.3 g/day Yes N/A Gliadin and Ret Abs not significantly different between oats and controls No increase in IELs among subjects in remission with and without oats IELs decreased among new Dx subjects with and without oats Results strengthen the view that most subjects tolerated oats in the amounts of 50-70 g/day in an otherwise GFD... 

The use of buspirone in social phobia has also been investigated by Schneier et al. [1993]. In this 12-week open trial, 21 patients who met DSM-III-R criteria for social phobia and did not display a response during a 1 -week placebo run-in, went on to receive buspirone. The drug was initiated at 5 mg three times a day and was increased by 5 mg/day every 3 days to a maximum dosage of 60 mg/day or until side effects prevented further dose increases. Seventeen patients completed the trial. At the end of week 12, 8 [47%] of the 17 subjects were rated as much to very much improved on the Clinical Global Impression Scale (Guy 1976]. Of those subjects tolerating doses of 45 mg/day or more, 67% [9/12] were at least much improved. ... 

A best guess is that a supportive atmosphere and careully screened and well-informed (with respect to experimental procedures, goals, pitfalls, etc.) subjects were important in determining how well these volunteer subjects tolerated the experiments. 

Meyer-Lindenberg, A., Rammsayer, T., Ulferts, J., Gallhofer, B. The effects of sulpiride on psychomotor performance and subjective tolerance. Eur. Neuropsychopharmacol. 7, 219-223, 1997. 

Rammsayer, T. Gallhofer, B. 1995, Remoxipride versus haloperidol in healthy volunteers psychometric performance and subjective tolerance profiles, Int.Clin.Psychopharmacol., vol. 10, no. 1, pp. 31-37. 

Voruganti, L., Cortese, L., Oyewumi, L., Cernovsky, Z., Zirul, S., 8c Awad, A. (2000). Comparative evaluation of conventional and novel antipsychotic drugs with reference to their subjective tolerability, side-effect profile and impact on quality of life. Schizophrenia Research, 43, 135-145. 

EPP were performed before and after administration of the drug. Ch was also monitored in sone cases. All subjects tolerated these procedures very well, and there were reportedly no untoward effects of the drugs in any of the subjects tested. 

Brunner H, Grabner G. Subjektive Vertraglichkeit des Pentagastrmtests. [Subjective tolerance of pentagastrin test.] Leber Magen Darm 1978 8(3) 165-9. 

Gyllfors P, Bochenek G, Overholt J, et al. Biochemical and clinical evidence that aspirin-intolerant asthmatic subjects tolerate the cyclooxygenase 2-selective analgesic celecoxib. J Allerg Clin Immunol 2003 111 1116-1121. 

Zaleplon (usually administered in 5-, 10-, or 20-mg doses) has been studied in clinical trials of patients with chronic or transient insomnia. Studies have focused on its effects in decreasing sleep latency. Zaleplon-treated subjects with either chronic or transient insomnia have experienced shorter periods of sleep latency than have placebo-treated subjects. Tolerance to zaleplon does not appear to occur, nor do rebound insomnia or withdrawal symptoms after stopping treatment. 

Rosenberg, D.E. etal, 1964. The effect of N,N-dimethyltryptamine in human subjects tolerant to lysergic acid diethylamide Psychopharmacologia 5 217-227. 

In human plasma, aclidinium is subjected to rapid hydrolysis to inactive metabolites, suggesting that adidinium may have less systematic adverse side-effects [67 ]. In an early safety study, 16 healthy subjects tolerated adidinium well, without significant adverse effects using drug doses up to 6000 gg [ ]. In another open-label study based on 24 subjects, there was not an association between different levels of kidney disease and increased drug levels of adidinium in the plasma. This was attributed to its rapid plasma hydrolysis [69 ]. Consequently, aclidinium can safely be used in patients witii kidney disease. 

The results showed no clinical relevant effect of a heparin containing anticoagulation in terms of an increase in overall CD34+ cell collection during LVL, although this regimen had some benefits in the incidence and subjective tolerance towards AR. Based on the results, the decision between a citrate- and heparin-substituted anticoagulation for LVL should be driven by patient-related factors, and potential contraindications of both methods should be considered. 

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