Pharmacokinetics of tenoxicam in healthy human volunteers

Tenoxicam, a thieno-thiazine derivative, belongs to a new chemical class of non-steroidal anti-inflammatory drugs. Single dose kinetics was investigated after intravenous and oral administration to define the disposition and general absorption characteristics of the drug. After intravenous administration of 20 mg tenoxicam to 12 volunteers the time course of the plasma concentrations of unchanged drug followed two-compartment model characteristics. The area under the plasma-concentration time curve in the distribution phase contributed however only 3% or less to the total area. The plasma clearance was low with values ranging from 1.3 to 4.2 ml/min and the volume of distribution Vss was small averaging at 20 to 40% of the total body weight. The median half-life of elimination from the body was found to be 72 hours (range 42 to 100 hours). The disposition was not influenced by sex. Tenoxicam is highly bound to plasma albumin. At pH 7.4 the fraction bound exceeded 99% but was highly dependent on the pH. Plasma protein binding in patients with rheumatic disease was not different from that measured in healthy volunteers. The partitioning of tenoxicam into red blood cells was limited. Erythrocyte concentrations were only 20-30% of the corresponding plasma concentrations. After oral administration of a 20-mg tablet complete and rapid absorption of the drug was observed with maximum plasma levels of 1.7 to 3.6 micrograms/ml reached within 0.5 to 2 hours. Due to the rapid absorption and terminal half-life of the drug its plasma concentration profile after oral administration was very similar to that following intravenous dosing. The pharmacokinetic characteristics of tenoxicam offers a rationale to administer the entire dose in one single portion.