Plasma and whole blood pharmacokinetics of topiramate: the role of carbonic anhydrase

Because CA-I and CA-II are highly concentrated in erythrocytes, a large portion of TPM in whole blood is bound and serves as a depot. This contributes to the lower oral clearance (CL/F), apparent volume of distribution (Vss/F) and longer half-life (t1/2) that TPM has in blood compared to the CL/F, Vss/F and t1/2, estimated from plasma data. The difference between TPM blood and plasma pharmacokinetics was more profound at low doses (≤100 mg/day).