Pharmacokinetics of intravenous and rectal ketoprofen in young children.

OBJECTIVE: To evaluate the relative bioavailabilities of ketoprofen after intravenous and rectal administration to young children. DESIGN: Open-label prospective parallel-group study. PATIENTS: Participants were 28 children aged 7 to 93 months. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Diffusion of ketoprofen into the cerebrospinal fluid of young children.

BACKGROUND: The objective was to examine whether or not ketoprofen enters the cerebrospinal fluid after a single oral dose of 1 mg.kg-1 syrup, and to find out what is the lowest plasma concentration that will achieve a measurable level in the cerebrospinal fluid. METHODS: We measured ketoprofen concentrations both in plasma and cerebrospinal fluid of 10 young and healthy children (aged 9-86 months) after surgery with spinal anaesthesia. Samples of cerebrospinal fluid were collected 30 min after drug administration, at the same time as venous blood samples. A validated high-performance liquid chromatography method with a lower limit of 0.02 microg x ml(-1) was used to detect ketoprofen concentrations in cerebrospinal fluid and plasma. RESULTS: Ketoprofen was detectable in the cerebrospinal fluid only in the child who had the highest plasma concentration, 7.4 microg x ml(-1), while at plasma concentrations 6.5 microg x ml(-1) or less, cerebrospinal fluid (CSF) concentrations remained unmeasurable. The detected CSF/plasma ratio was 0.008. CONCLUSIONS: These results indicate that ketoprofen at a dose of 1 mg x kg(-1) is too low to produce measurable CSF levels within 30 min of oral administration.