Maximum life span potential

Species Scaling Adjusting for Maximum Life Span Potential... 

The consideration of clearance in units of volume per maximum life span potential, instead of the traditional volume per weight, provides an allometric relationship for drugs such as antipyrine and phenytoin [17]. Both of these dmgs are essentially low clearance compounds, cleared by P450 metabolism. Ultimately, the successful utility of such factors may be purely serendipitous as they simply exploit unique features of man as a species. 

A correlation was also presented between life-span and (Cu,Zn)- plus (Mn)-SOD activities of two strains of Drosophila melanogaster. The short-living vestigial strain had an activity of 72% on the average of the wild strain With 2 rodent and 12 primate species there was a good correlation between the ratio of SOD activity to specific metabolic rate and the maximum life-span potential for the brain, heart, and liver... 

Comparison of tissue susceptibility to oxidative protein damage, manifested as protein carbonylation in response to acute oxidative stress induced by exposure to X-rays, has shown that brain homogenates from 22-month-old rats were more susceptible to oxidative stress than those from 3-month-old rats. The brain was more susceptible to oxidative damage than the heart. A comparison of brain and heart homogenates susceptibility to acute oxidative stress in five different species (mouse, rat, rabbit, pig, and pigeon) indicated that maximum life-span potential of the species was related directly to their ability to control oxidative damage (Al). 

At. Agarwal, S., and Sohal, R. S., Relationship between susceptibility to protein oxidation, aging, and maximum life span potential of different species. Exp. Gerontol. 31, 365—372 (1996). 

Method II If the exponent lies between 0.7 and 1.0, the allometric equation for predicting clearance is normalized according to the maximum life span potential for each animal species, as initially proposed by Boxenbaum (7). 

Fig. 3.5 Allometric relationship between unbound antipyrine intrinsic clearance (C/U(int)) per maximum life-span potential (MLP) and body weight. Note that the body weight exponent of the regression equation is close to unity. Units on the ordinate (litres per MLP) are equivalent to C/U(int) (L/min) x MLP (min). (Reproduced with permission from Boxenbaum (1982).)...

Table 3.13 Body weight, brain weight and the calculated maximum life-span potential (MLP) for various mammalian species.

The use of half-life incorporates the variables that can influence the rate of drug elimination, those that affect distribution and clearance, whereas the use of systemic clearance focuses on the process of elimination, and corrections can be made for the extent of binding to plasma proteins and for estimated maximum life-span potential. Corrections seem to be justifiable when the human is included in the interspecies scaling technique. The necessity to apply correction factors, however, detracts from the use of allometric scaling for predicting the values of pharmacokinetic parameters. 

WT is actual body weight MLP is the Maximum Life span Potential CL=TVCL EXP(ETA(1))... 

Furthermore, Fig. 3 includes a state of the art Weibull distribution Fwoii) fit according to equation (1), the parameters to = 40586 km, T = 138587 km and b = 1,209 were determined with the maximum likelihood method (Birolini, A. 2007 Meyna, A. Pauli, P. 2003). However, the Weibull distribution is not able to describe the supposed complex mix of damage causes, of course, even qualitative deviations are present. The absolute deviation between damage probabdity based on real damage data and predicted potential pump damage based on Fwu(t) is about 12%, cf. Fig. 3 see life-span area (190-210) 103km. 

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