Gender as a covariate

From VPIOTROV@janbelc1.ssw.jnj.com Fri Jun 13 00:44:01 1997 Subject: Gender as a covariate Any body size parameter is gender-dependent, therefore, if a typical value of CL is dependent on WT, it will be automatically gender-dependent. However, to my experience, you will hardly find any `pure' gender effect on CL: if you plot Bayesian estimates of CL vs. WT and use different symbols for females and males, all points will lie along the same line (points corresponding to females will only be shifted towards smaller weigth). Moreover, including in the model gender as a separate covariate affecting CL most probably will not improve the fit. The situation with V is different. You may easily find V weight- AND gender-dependent. I.e., on the V vs. WT plot you may see two clusters: points corresponding to females will lie above those corresponding to males. Accordingly, having separate THETAs for males and females in the model will substantially improve the fit. An explanation is quite simple: if the drug is lypophilic (most drugs are) it tends to distribute in adipose tissues, and fat contents in females is known to be higher (on average) than in males. Vladimir Piotrovsky, Ph.D. Janssen Research Foundation Clinical Pharmacokinetics vpiotrov@janbelc1.ssw.jnj.com B-2340 Beerse Belgium Fax: +32-14-605834 Email: vpiotrov@janbe.jnj.com