The influence of gastric emptying on droxicam pharmacokinetics.
Droxicam is a new nonsteroidal anti-inflammatory drug that is a pro-drug of piroxicam. The influence of gastric emptying rate on droxicam pharmacokinetics has been investigated in eight healthy male volunteers. A single, 20 mg dose was administered p.o. together with 1500 mg of paracetamol. Gastric transit was experimentally modified by administration of propantheline (45 mg, p.o.) or metoclopramide (10 mg, i.v.) simultaneously with the droxicam and the paracetamol. Plasma levels of paracetamol were used as markers of gastric transit. The plasma concentrations of piroxicam, the active substance from droxicam, were determined by a high-performance liquid chromatographic method. The pharmacokinetic parameters of droxicam were: Cmax = 1.03 +/- 0.16 micrograms/mL (mean +/- SD). Tmax = 11.1 +/- 5.7 hr, AUC = 115.7 +/- 29.6 micrograms hr/mL, T 1/2 a = 2.64 +/- 0.72 hr. T 1/2 el = 73.6 +/- 16.7 hr, CL/F = 3.06 +/- 0.80 mL/min and MRT = 111.1 +/- 23.5 hr. Following modification of gastric emptying, only Tmax (droxicam + metoclopramide = 25.0 +/- 10.8 hr and droxicam + propantheline = 20.8 +/- 8.8 hr) underwent significant change (P less than 0.05). These results indicate that absorption rate of droxicam has been modified but bioavailability does not suffer modification in conditions of altered gastric emptying.
Department of Clinical Research, Laboratorios Dr. Esteve, S. A., Barcelona, Spain.
J
J
Sánchez
L
L
Martínez
J
J
García-Barbal
R
R
Roser
A
A
Bartlett
R
R
Sagarra
D000082:Acetaminophen / Q000097:blood; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004992:Ethics, Medical; D005746:Gastric Emptying; D006801:Humans; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D010894:Piroxicam / Q000097:blood; D011413:Propantheline / Q000494:pharmacology; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011725:Pyridines; D011413:Propantheline; D010894:Piroxicam; D000082:Acetaminophen; C049073:droxicam; D008787:Metoclopramide