Pharmacokinetics of free and total XXXX in adolescents and young adults during maintenance therapy.

@entity1092 @entity2052
The pharmacokinetics of total and free @entity1092 ( @entity2052 ) in plasma and whole blood was investigated in seven adolescents and young adults (mean age 17.3 years) during a dosage interval at steady state. The concentration curves of @entity2052 in whole blood after an oral morning dose (mean 8.2 mg/kg body wt.) closely followed those in plasma but at a reduced level. The apparent volume of distribution (Vd) of total @entity2052 was 0.150-0.197 l/kg body wt. and of free @entity2052 0.911-1.58 l/kg body wt., which indicates considerable distribution of unbound @entity2052 as well as drug binding to extravascular proteins. The terminal half-life of free @entity2052 (6.4-6.7 h) was significantly shorter (P less than 0.05) than the half-life of total @entity2052 (10.4-11.9 h). The binding of @entity2052 in plasma was concentration dependent and fluctuated considerably within the individual dosage intervals. Concentrations of unbound @entity2052 in plasma water of whole blood varied to a corresponding degree, since distribution to blood cells was low (mean 2.2%). It is concluded that there are substantial differences in the pharmacokinetics of free and total @entity2052 . This may contribute to the well-known poor correlation between dose, plasma concentrations and effect of @entity2052 .
