Influence of gastric acid secretion blockade and food intake on the bioavailability of a potassium diclofenac suspension in healthy male volunteers.
The bioavailability of a single dose of a potassium diclofenac (KDIC) suspension (Flogan, Merck, 7ml, 105 mg) was studied in 13 healthy male volunteers in the fasting state (placebo phase, PLA), after gastric acid secretion blockade (subacute pretreatment with omeprazole, OME phase) and after food intake (FOOD phase). A 14-day washout period between phases was adopted. Serum samples were obtained over a 24 hour interval and the diclofenac concentrations were determined by high pressure liquid chromatography with ultraviolet detection. From the serum diclofenac concentration vs time curves, the AUC[0-infinity] (area under the concentration vs time curves from 0 to infinity), Cmax (maximum achieved concentration), tmax (time to achieve Cmax), Ke (terminal first order elimination constant), half-life values (t1/2) and AUC[0-infinity]/t1/2 ratio as an index of diclofenac clearance, were obtained. All these variables were analyzed using both parametric and non-parametric statistics. In the presence of food, KDIC absorption was delayed (as shown by lower Cmax and greater tmax values) and decreased (as shown by lower AUC[0-infinity] values), and the serum diclofenac concentration vs time curves showed a biphasic pattern. Omeprazole pretreatment did not change the absorption parameters. Both of these treatments altered the diclofenac clearance, as assessed by the AUC[0-infinity]/t1/2, t1/2 and Ke values, although the changes were not considered to be clinically significant, because of the wide therapeutic range for diclofenac. The delay in the rate of diclofenac absorption produced by food intake was not due to an increase in the gastric pH, and could be of particular importance when rapid analgesia is desired.
Poli
A
A
Department of Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina, Florianopolis, Brazil.
Moreno
R A
RA
Ribeiro
W
W
Dias
H B
HB
Moreno
H
H
Muscara
M N
MN
De Nucci
G
G
D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D004008:Diclofenac / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004435:Eating; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000494:pharmacology*; D012016:Reference Values; D013270:Stomach / Q000187:drug effects*; D013535:Suspensions
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D013535:Suspensions; D004008:Diclofenac; D009853:Omeprazole