Pharmacokinetics of intravenous and rectal ketoprofen in young children

To evaluate the relative bioavailabilities of ketoprofen after intravenous and rectal administration to young children. Open-label prospective parallel-group study. Participants were 28 children aged 7 to 93 months. Eighteen children received a single intravenous injection of ketoprofen 1 mg/kg, and ten children, weight 16-24 kg, received a 25mg ketoprofen suppository. Venous blood samples were collected at selected times after administration, ranging from 2 minutes to 8 hours for the intravenous group and from 30 minutes to 8 hours for the suppository group. A validated high performance liquid chromatography method was used to measure plasma ketoprofen concentrations. In the intravenous group, the maximum plasma concentration of ketoprofen ranged between 10.5 and 22.2 mg/L, and in the suppository group, following dose normalisation to 1 mg/kg of ketoprofen, between 3.8 and 7.4 mg/L. In the intravenous group, area under the concentration-time curve from zero to infinity ranged between 9.2 and 23.5 mg x h/L, and in the suppository group after dose normalisation between 8.8 and 12.9 mg x h/L. The bioavailability of ketoprofen from the suppository was about 73%. Volume of distribution was 0.04-0.10 L/kg in the intravenous group and 0.08-0.16 L/kg in the suppository group. The terminal half-life was comparable in both study groups, ranging between 0.7 and 3.0 hours in the intravenous group and between 1.2 and 2.9 hours in the suppository group. Absorption of ketoprofen after rectal administration is reasonably rapid and predictable. Because the bioavailability of rectal ketoprofen is also relatively high, a suppository may be used in children in whom the drug cannot be given intravenously or by mouth.