Does body weight matter?

It would appear, not very much. After all drug doses are seldom adjusted for body weight. Only in situations where the therapeutic index is very low, such as for oncologicals, is the drug dose adjusted for body weight. Clearance as a pharmacokinetic parameter, is seldom denominated by body weight.

Often when discussing differences in PK between populations, you can almost hear the sigh of relief when the differences in AUC can be discounted by body weight. Suddenly it's like the differences should not matter any more.

So should body weight matter?

The answer to my mind is, yes.

Pharmacokinetically, body weight does not matter as much to clearance as it does to distribution. For this reason Vd is often denominated by body weight. But not so clearance. The general reluctance to consider body weight as a major determinant of drug effect related to an older line of reasoning where drug response is seen primarily as a function of AUC, steady state concentrations and consequently clearance, rather than Vd. But as pointed out in previous posts, Vd changes can have considerable effects on drug PK, particularly Cmax and trough concentrations. These are less considered mainly because of their relative instability compared to steady state concentrations. It is however possible that variability in drug responses may in fact be more sensitive to changes in Cmax and troughs rather than steady state concentrations. If so, Vd effects may be potentially more profound than have been previously thought.

Why does this reality bother us?

Principally because one of the immediately noticeable differences between our Asian population and Western population is the difference in body weights. Caucasian males may have an average body weight of 85 kg as compared to age matched Chinese males of 65 kg. Chinese females would have an average of about 55 kg. If one recognizes that drug response may be affected by body weight, it would make us serious reconsider if drug dosage regiments developed from studies involving healthy Caucasian males, may be easily applied to Chinese females without adjustments to the average of 35% lesser body weight.

And this is not yet even considering differences in lean body mass, especially since Chinese/Asians have much less lean body mass for a given body weight, when compared to Caucasians.