Re: Time of day as a covariate

From: Joel S. Owen - joel.owen@cognigencorp.com Subject: Re: [NMusers] Time of day as a covariate Date: 2/11/2004 7:17 PM Hi Pete, In addition to the traditional consideration of changes in plasma protein binding, one might also consider fluctuation in binding to other bio-molecules which might have diurnal variation. Examples of time-of-day variation in hormonal regulation and DNA synthesis are given in: Borst DW, Mahoney WB. Diurnal changes in mouse mammary gland DNA systhesis. J Exp Zool. 1980 Nov;214(2):215-218. Schell, H, Schwarz W, hornstein OP, Bernlochner W, Weghorn C. Evidence of diurnal variation of human epidermal cell proliferation. I. Epidermal 3H-labeling index and serum cortisol rhythm. Arch Dermatol Res. 1981:271(1):41-47 We have used such a consideration as a modeling approach in which time-dependent variation in Rmax was introduced into a model of target mediated pharmacokinetics such as described (without dirunal variation) in Mager DE, Jusko WJ. General Pharmacokinetic Model for Drugs Exhibiting Target-Mediated Drug Disposition. J Pharmacokinet Pharmacodyn 2001. 28:507-532. Best regards, Joel -- Joel S. Owen, Ph.D. Director PK/PD Cognigen Corporation 395 S. Youngs Road Buffalo, NY 14221 (v) (716) 633-3463 ext. 247 (f) (716) 633-7404 (e) joel.owen@cognigencorp.com http://www.cognigencorp.com/ _______________________________________________________