Celecoxib distribution

C. Pharmacokinetics. NSAIDs are generally well absorbed, and volumes of distribution (Vd) are relatively small (eg, 0.15 L/kg for ibuprofen). COX-2 inhibitors have larger volumes of distribution (86-91 L in adults for rofecoxib, 400 L for celecoxib). Most agents are highly protein bound, and most are eliminated through hepatic metabolism and renal excretion with variable half-lives (eg, 1.5-2.5 hours for ibuprofen and 12-17 hours for naproxen). (See also Table 11-59.)... 

Fig. 5. Flow cytometric analysis of intracellular Ca + [Ca +]i in celecoxib-treated PC-3 cells. (A) Representative diagrams depicting cellular distribution of [Ca +]i in PC-3 cells before (t = 0) and 36 s after exposure to 50 pM celecoxib. (B) Dose- and time-dependent effect of celecoxib on [Ca +]i. lndo-1-loaded PC-3 cells were treated with different levels of celecoxib, ranging from 0 to 100 pM, and were subjected to flow cytometric Ca analysis as described in the Materials and Methods. Source Reprinted from Reference 74 with permission from Elsevier.

Celecoxib is extensively distributed in tissues and is 97% protein-bound. It is bound primarily to albumin and to a lesser extent alpha-1-acid glycoprotein. The approximate volume of distribution at steady state is 400 liters, suggesting extensive distribution into the tissues. This extensive volume of distribution may be related to the lipophilic nature of celecoxib as well as to its high PKa (11.1). The effective plasma is approximately 11 hours under fasting conditions [1]. 

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