Pharmacokinetics of isoxicam following intravenous, intramuscular, oral and rectal administration in healthy volunteers.

Abstract

1 The pharmacokinetic characteristics and bioavailability of isoxicam were investigated in healthy male volunteers following various routes of administration. Plasma concentrations were determined up to 96 or 120 h following each administration using a selective h.p.l.c. method. 2 Twelve subjects received an i.v. and an i.m. injection of 150 mg and an oral dose of 200 mg (two capsules) in a three‐way crossover design. 3 The plasma concentration‐time curves after intravenous administration followed two compartmental characteristics with a rapid initial distribution phase and a predominant terminal elimination phase. The area under the distribution phase contributed only 0.4% to the total AUC. Mean disposition parameters were: t1/2, lambda 1 = 3.3 min t1/2, lambda z = 28 h, Vc = 5.61, Vdarea = 12.71, CL = 5.1 ml min‐1. 4 Following other routes of administration, the isoxicam plasma profile could be adequately described by a one compartment model. 5 After the i.m. dose, isoxicam was rapidly and completely absorbed: within 15 min 40% of the peak concentrations were attained. Maximum plasma concentrations of 11.7 micrograms ml‐1 were reached after an average of 3 h. 6 After oral administration isoxicam was completely bioavailable. Mean peak concentrations of 12.3 micrograms ml‐1 were obtained within 10 h. 7 The bioavailability of suppositories containing 200 mg of active substance was investigated in another 10 volunteers relative to capsules (2 × 100 mg). The formulations tested were bioequivalent with respect to the amount absorbed. 8 Comparison of AUCs (normalized for dose and body weight) resulting from all treatments, did not show significant differences among the various formulations.(ABSTRACT TRUNCATED AT 250 WORDS)