title: The effect of metoclopramide on the absorption of tolfenamic acid.
abstract: The effect of metoclopramide on the absorption of orally given tolfenamic acid (300 mg) was investigated using rectal metoclopramide hydrochloride (20 mg) pretreatment in a randomized crossover study in eight voluntary migraine patients when headache-free. Tolfenamic acid and metoclopramide serum concentrations were estimated by high-performance liquid chromatograhic (HPLC) methods using UV detection. Metoclopramide given 30 min prior to tolfenamic acid significantly increased serum tolfenamic acid levels at 45 and 60 min after ingestion, compared to the levels obtained with placebo pretreatment. The bioavailability of tolfenamic acid, measured as the area under the serum tolfenamic acid concentration-time curve (AUC0-5 h) and the peak concentration, was not influenced by metoclopramide. The peak concentration of tolfenamic acid was 4.1 +/- 0.9 micrograms/ml (mean +/- s.e.m.), the time peak 1.9 +/- 0.2 h, and the elimination half-life 2.3 +/- 0.5 h calculated from the values without metoclopramide. The peak concentration of metoclopramide was 69 +/- 6.3 ng/ml and the time to peak 118 +/- 29 min. The results suggest that rectal metoclopramide enhances the rate of absorption of tolfenamic acid without changing its bioavailability.
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D008787:Metoclopramide / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D062367:ortho-Aminobenzoates / Q000378:metabolism*
chemical_list: D062367:ortho-Aminobenzoates; C009500:tolfenamic acid; D008787:Metoclopramide