Subject dosing

Roache, J. and Griffiths, R., Interaction of diazepam and caffeie Behavioral and subjective dose effects in humans. Pharmacology, Biochemistry and Behavior 26(4), 801-812, 1987. 

There are only two reports of the human evaluation of a 6-hydroxylated N,N-dialkyltryptamine. Szara and Hearst (223) studied the effects of 6-hydroxy-N,N-diethyltryptamine (6-OH-DET 56) in a single subject. Doses of 1 and 2 mg were inactive a 5-mg dose produced a short-lasting perceptual disturbance and a 10-mg dose, after 1 hr, produced some psychotomimetic disturbances. Rosenberg et al. (182) compared the activity of DMT with that of 6-OH-DMT (55) in five human subjects. While DMT was active, the 6-hydroxy derivative was found to be inactive at intramuscular doses of approximately 50 to 75 mg. At a dose of 10 mg/kg, 6-OH-DMT (55) increased spontaneous activity in mice more so than a comparable dose of DMT 6-OH-DET (36) was essentially equiactive with DET in this respect (224). In most other animal studies, however, 6-hydroxylation of DMT has been observed to result in a decrease or complete loss of behavioral activity (228,236-238). The behavioral potency of 5-OMeDMT (59) was also reduced by 6-hydroxylation (226). 7-Hydroxy-N,N-dimethyltrypt-amine (7-OH-DMT 57) has not been evaluated in man. At an intraperitoneal dose of 33 jtM/kg, 7-OH-DMT displayed no behavioral effects in rats (228). The pharmacologic effects of all four hydroxylated derivatives of DMT, psilocin (49), bufotenine (53), 6-OH-DMT (55), and 7-OH-DMT (57) have been compared in studies by Taborsky et al. (228) and by Cerletti et al. (29). 

Efficacy—Clinical studies in human subject (dose response, carcinogenicity,... 

Table 7. Compiled totals of subjects tested with EA 3443 by number of subjects, dose, route of administration and number of hours observed...

Number of Subjects Dose (mcg/kg) Food Intake (cal.) mean S.E. Fluid Intake (ml) mean S.E. Sleep Duration (h) S.E. 

Cunan, H. V. et al., Cognitive and subjective dose-response effects of acute oral A9-tetrahydrocannabinol (THC) in infrequent cannabis users, Psychopharmacology, 164, 61, 2002. 

The recommended dose of modafinil is 200 mg/day for the treatment of excessive daytime sleepiness associated with narcolepsy however, doses of 400 mg/day are FDA-approved. While there is evidence that the higher dose is well tolerated, it has not been established that it confers additional therapeutic benefit (196). In sleep-deprived subjects, doses of 600 mg/day have been administered, but the preponderance of evidence suggests that 300M00 mg/day is probably sufficient and less likely to produce unwanted side effects. 

Definition of daily dose levels maximum dose for each subject, dose with the longest exposure for each subject, mean daily dose, cumulative dose. 

Figure 6.3 Quantal effects. Typical set of data after administration of increasing doses of drug to a group of subjects and observation of minimum dose at which each subject responds. Data shown are for 100 subjects dose increased in 0.2 mg/kg of body weight increments. Mean (ji) (and median) dose is 3.0 mg/kg standard deviation (v) is 0.8 mg/kg. Results plotted as histogram (bar graph) showing number responding at each dose smooth curve is normal distribution function calculated for ji of 3.0 and v of 0.8.

Tibben, M.M., Rademaker-Lakhai, J.M., Rice, J.R., Stewart, D.R., Schellens, J.H.M., Beijnen, J.H. Determination of total platinum in plasma and plasma ultrafiltrate, from subjects dosed with the platinum-containing N-(2-hydroxypropyl)methacrylamide copolymer AP5280, by use of graphite-furnace Zeeman atomic-absorption spectrometry. Anal. Bioanal. Chem. 373, 233-236 (2002)... 

Study Design Number Number of Subjects Dose Levels Power Comments... 

Summary statistics include those subjects Dose 6. 

Tracer in milk Adults (5) 11 Healthy subjects. Dose administered in milk, daily for 21-32 days. Absorption estimated from whole body retention kinetics. Rundo and Lilligraven 1966... 

Fig. 3. (A) Serum levels and (B) urinary excretion after oral administration of clarithromycin and erythromycin to healthy volunteers. O, clarithromycin [ , erythromycin stearate. Each value represents the mean S.E. of six subjects. Dose 200 mg/man. (From Saito et al. [53j, Fig. 3, p. 527.)...

Species No. subjects Dose" Matrix Sampling time (h) Recovery (% of dose) Total recovery (% of dose)... 

Personal samplers are those for continuously monitoring exposure of persons to hazardous air-borne substances in the living and/or occupational environment. These samplers are often used in surveys to measure personal exposure to air pollutants and thus to calculate subjects doses from their respiration and living patterns. Personal samplers may be categorized as either active or passive. 

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