Potency, relative, estimation

Conversion from parenteral morphine or other opioids (parenteral or oral) to CR/ER/SR doseforms- Exercise particular care in the conversion process. Because of uncertainty about, and intersubject variation in, relative estimates of opioid potency and cross-tolerance, initial dosing regimens should be conservative that is, an underestimation of the 24-hour oral morphine requirement is preferred to an overestimate. To this end, estimate initial individual doses conservatively. In patients whose daily morphine requirements are expected to be 120 mg/day or less, the 30 mg tablet strength is recommended for the initial titration period. Once a stable dose regimen is reached, the patient can be converted to the 60 or 100 mg tablet strength, or appropriate combination of tablet strengths, if desired. Conversion from CR/ER/SR oral morphine to parenteral opioids - It is best to assume that the parenteral-to-oral potency is high. For example, to estimate the required 24-hour dose of morphine for IM use, one could employ a conversion of 1 mg morphine IM for every 6 mg of morphine... 

In the absence of human or animal oral dose-response data, the relative potency approaches developed by Watson et al. (1989) and U.S. EPA (1991) are considered to be appropriate methods for estimating the tnmorigenic potency of sulfur mustard by the oral route of exposure. The oral slope factor derived by Watson et al. is approximately one order of magnitude less than the one derived from the relative potency estimated by U.S. EPA (1991). In the emerging area of relative potency analysis, a factor of 10 difference represents a good fit. There is no significant difference between the estimates of sulfur mustard carcinogenic potency relative to B(a)P pnblished by Watson et al. (1989) and U.S. EPA (1991). 

Spectrophotometric deterrnination at 550 nm is relatively insensitive and is useful for the deterrnination of vitamin B 2 in high potency products such as premixes. Thin-layer chromatography and open-column chromatography have been appHed to both the direct assay of cobalamins and to the fractionation and removal of interfering substances from sample extracts prior to microbiological or radioassay. Atomic absorption spectrophotometry of cobalt has been proposed for the deterrnination of vitamin B 2 in dry feeds. Chemical methods based on the estimation of cyanide or the presence of 5,6-dimethylben2irnida2ole in the vitamin B 2 molecule have not been widely used. 

Tests of general application. In addition to the tests designed to estimate the potency and to exclude the hazards peculiar to each vaccine there are a number oftests of more general application. These relatively simple tests are as follows. 

Several attempts have been made to estimate the dose required in humans in relation to a drug s potency, and to put this into the context of solubility and permeability for an optimal oral drug [2, 3]. A relatively simple example of this is where a 1.0 mg kg-1 dose is required in humans, then 52 pg mL"1 solubility is needed if the permeability is intermediate (20-80%) [3]. This solubility corresponds approximately to 100 pM of a compound with a MW of 400 g mol-1. Most screening activities for permeability determinations in, e.g., Caco-2, are made at a concentration of 10 pM or lower due to solubility restrictions. The first implication of this is that the required potency for these compounds needs to correspond to a dose of <0.1 mg kg-1 in humans if the drug should be considered orally active. Another implication would be the influence of carrier-mediated transport (uptake or efflux), which is more evident at low concentrations. This could result in low permeability coefficients for compounds interacting with efflux transporters at the intestinal membrane and which could either be saturated or of no clinical relevance at higher concentrations or doses. 

Basketter, D.A., et al., Use of the local lymph node assay for the estimation of relative contact allergenic potency. Contact Dermatitis, 42, 344, 2000. 

By inspection, atropine s effects on cognitive (NF) performance reach a maximum at about 4 hours (Fig. 60). The estimated MED50 is about 90 mcg/kg and the ID50 is about 160 mcg/kg. Onset time (Tonso) and duration (D50) at the IDso.are about 1 and 6 hours respectively. The relative central potency of atropine is the lowest of any of the belladonnoids we studied (Fig. 74). Once again, as is the case with BZ vs. EA 3167 and EA 3443 vs. EA 3580, a minor structural change makes a major difference. 

Since LSD would be released as an aerosol if used in a military setting, we devoted considerable effort to estimating its relative potency by the inhalation route. Two forms of the drug the maleate salt (black circles) and the free base (white) were compared (Fig. 95). There appeared to be no difference between the two salts in their effects on NF performance. 

Estimates of Carcinogenic Potencies of Various PAH, Relative to Benzo[a]pyrene (BaP)... 

Thorslund, T.W. and D. Farrar. 1990. Development of relative potency estimates for PAH and hydrocarbon combustion product fractions compared to benzo[a]pyrene and their use in carcinogenic risk assessment. EPA/600/R-92/134, Dept. Commerce, NTIS. 

Utilizing the dose-ratio (relative potency) data that we obtained for GT-1 and GT-2, we constructed constrained Schild plots to obtain an estimation of the pA2 (= -log apparent affinity constant). An estimation of the p 2 values is indicated by the intercept of a best fit line of slope of -1 (Figure 5). 

Kenakin, T. P., and Morgan, P. H. (1989). Theoretical effects of single and multiple transducer receptor coupling proteins on estimates of the relative potency of agonists. Mol. Pharmacol. 35, 214-222. 

---