Geometric mean ratio

Based on geometric mean ratio of echinacea to control. 

Results of drag-drag interaction studies should be reported as 90% confidence intervals about the geometric mean ratio of the observed pharmacokinetic measures with (S+I) and without the interacting drug (S). Confidence intervals provide an estimate of the distribution of the observed systemic exposure measure ratio of S+I versus S alone and convey a probability of the magnitude of the interaction. 

In the case where the upper limit of the 90% Cl (equation 4) falls exactly on the upper preset BE limit, Diff becomes equal to Diffmax, which is the maximum acceptable difference between means (25,39). Diff ax, and therefore the maximum acceptable geometric mean ratio (OMR ax) [OMR ax = exp(Diffn,ax)]. for a given... 

The major feature of the definition of classic unsealed ABE relies on the fact that two constant borderline values (0.80 and 1.25) are assigned for BE limits. Under this condition, extreme geometric mean ratio (GMR) values, which ensure BE, converge at unity as intrasubject variability increases (25,40). In other words, when upper and lower BE limits are fixed, the demonstration of BE requires that the means of two products must be as close as possible as variability increases. Although setting constant the BE limits is conceptually fundamental, the 0.80 to 1.25 limits appear very strict in the case of HV drugs. To overcome the difficulties encountered in the assessment of the bioavailabUity of HV drugs with the currently used BE limits, several approaches have been proposed. 

Figure 1 BE limits left side) and extreme GMR values, which ensure BE right side) as a function of within-subject variability (ANOVA CV), for the classic (0.80-1.25) limits dashed lines) and three proposed procedures solid lines) expanded BE limits beyond a switching variability CVo = 30% (24) top) BE limits with levelling-off properties based on a sigmoid function (63) middle) and scaled BE limits (equation 10) with a preset variabUity CVwo = 25.4% and switching variability CVq = 30% (35,64) bottom). A two-period crossover study with 36 subjects was assumed for (he calculation of extreme GMR values. Abbreviations BE, bioequivalence GMR, geometric mean ratio CV, coefficient of variation.

Karalis V, Macheras P, Symillides M. Geometric Mean Ratio-dependent scaled bioequivalence limits with leveling-off properties. Eur J Pharm Sci 2005 26 54-61. 

Fig. 1. Geometric mean ratios of the maximal treadmill walking distance (on the horizontal axes) and 95% confidence intervals for cilostazol as compared with placebo. Results of four randomized trials. From ref. 22, with permission.

Antimalarial drugs There were lower concentrations of atovaquone -I- proguanil in HIV-infected individuals taking efavirenz. The authors compared the pharmacokinetics of atovaquone -I- proguanil between healthy volunteers and HIV-infected patients taking efavirenz and found that the geometric mean ratio AUCo x for... 

Dienogest The effect of ketoconazole on pharmacokinetics of an oral contraceptive containing oestradiol valerate and dienogest was evaluated in 12 healthy volunteers using open-label, one-arm design [49 ]. Ketoconazole increased oestradiol valerate and dienogest systemic exposure (geometric mean ratio) 157% and 286%, respectively. 

For a symmetrical separation of component h from c, Brian Staged Cascades in Chemical Processing, Prentice-Hall, Englewood Cliffs, N.J., 1972) reported that the ratio of wash solvent to extraction solvent W /S should be set equal to the geometric mean of the two slopes of the equilibrium lines [Eq. (15-35)]. 

The equivalence margins for bioequivalence specified by both the FDA (2001) Statistical Approaches to Establishing Bioequivalence and the CPMP (2001) Note for Guidance on the Investigation of Bioavailability and Bioequivalence require that the ratio of the geometric means, for the two treatments lie between... 

The reason why ratios of geometric means are used in this context is as discussed in Section 11.4 the distributions of AUC and tend to be positively skewed and the log transformation is applied to recover normality. 

Protein hydrolysis in 6N HCl and subsequent analysis to determine amino acids (except tryptophan, which is acid labile) chemically present is a first step in protein quality evaluation. The chemical score and the EAA index represent attempts to use this information to chemically estimate nutritional quality of protein their obvious limitation is their disregard for amino acid availability. The chemical score is obtained by evaluating the percent of the limiting amino acid in comparison to that amino acid in whole egg protein ). The EAA index is the geometric mean of the ratios of each of the essential amino acids to those amino acids occurring in whole egg (4). 

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