Pharmacokinetics of tolfenamic acid in pediatric patients after single oral dose.

Abstract

The pharmacokinetics of tolfenamic acid, a non-steroidal anti-inflammatory drug, were determined following administration of a 1 mg/kg single oral dose of tolfenamic acid suspension to 6 feverish children. Their ages were from 2-14 years (mean 7.5 years) and their weights were from 12-50 kg (mean 29.2 kg). Tolfenamic acid produced a significant fall in temperature (about 2 degrees C) compared to the initial value before oral intake of the drug and was well tolerated without adverse effects. Blood samples for determination of tolfenamic acid concentrations in plasma were obtained at timed intervals for up to 8 h post-dose. Plasma concentrations of tolfenamic acid were determined using a reversed phase HPLC method and pertinent pharmacokinetic parameters were estimated by model-independent standard methods and were the following: the mean peak plasma concentration (Cmax +/- SEM) was 1.09 +/- 0.44 micrograms/ml (range, 0.65-1.63 micrograms/ml) and the mean time (tmax +/- SEM) to reach peak plasma concentration was 1.4 +/- 0.4 h (range, 0.5-3.0 h). The mean area under the plasma concentration-time curve (AUC0-->infinity +/- SEM) was 4.61 +/- 0.40 micrograms.h/ml (range, 2.74-5.98 micrograms.h/ml), the mean elimination half-life (t1/2 +/- SEM) was 2.82 +/- 0.21 h (range, 2.19-3.40 h) and the mean apparent total clearance (CL/F +/- SEM) was 3.83 +/- 0.41 ml/min/kg (range, 2.79-6.08 ml/min/kg).