Pentoxifylline (PTX) is proposed therapy for sickle cell disease (SCD), but previous studies have lacked a pharmacokinetic (PKN) basis for dose in children and hence weakened interpretation of efficacy. Also, distribution of PTX in SCD red blood cells (RBC) was not studied. The PKN of PTX in plasma and RBC of children with SCD were examined using a new liquid formulation of the drug. A Phase II PKN study was done in 10 children with SCD, ages 7-17 yr, at a single dose of 6 mg/kg. Each patient received a breakfast consisting of cereal, milk and juice 15-45 minutes prior to administration of drug. Blood samples were taken just prior to dosing and at 12 intervals thereafter for 6 hours. Concentrations of PTX and a major metabolite (M1) were determined in both the plasma and RBC fraction of each blood sample by HPLC analysis. The PKN parameters (mean ±SD) are shown in the table.

Table 1 No caption available.
Full size table

The average plasma/RBC ratio for PTX in SCD was similar to that found for in vitro studies of normal adult blood. The plasma Cmax is similar to that reported (Smith et al, J Pharm Sci, 1986) for fasted adults given 200 mg PTX as single dose and who showed an average t1/2 of 23 minutes. PTX and M1 are distributed to a greater extent in plasma than RBC, and show a similar T1/2 for respective drug in each fraction. The plasma PTX T1/2 is less than that for M1. These data now provide a basis for design of a PTX Phase III efficacy study in SCD children and reveal that both PTX and M1 can be measured in plasma for appropriate pharmacodynamic evaluations.

Student's unpaired, single-tailed “t”, P < 0.05 in comparing:

  1. 1

    PTX plasma vs PTX RBC

  2. 2

    M1 plasma vs M1 RBC

  3. 3

    PTX plasma vs M1 plasma

  4. 4

    PTX RBC vs M1 RBC