A 3-way crossover study to evaluate the pharmacokinetic interaction between nateglinide and diclofenac in healthy volunteers.
OBJECTIVE
To assess in healthy male volunteers (n = 18) the effect of diclofenac, a non-steroidal anti-inflammatory analgesic drug used for treatment of rheumatic diseases, on the pharmacokinetics of nateglinide, a new oral hypoglycemic agent that acts by a novel therapeutic mechanism to stimulate insulin release. The effects of nateglinide on the pharmacokinetics of diclofenac were also investigated.


METHODS
This open-label study was conducted as a randomized, 3-period, 6-sequence, crossover investigation consisting of 2 reference treatment periods (diclofenac 75 mg or nateglinide 120 mg, alone) and 1 test period (concomitant nateglinide and diclofenac). On the days when nateglinide was administered, subjects received a 120 mg dose at the start of the study day and a second 120 mg dose 4 h after the first. A 2 to 7-day washout interval separated each of the study periods. Nateglinide and diclofenac plasma concentrations were determined up to 12 and 24 h, respectively.


RESULTS
Administration of diclofenac did not alter the pharmacokinetics of nateglinide in healthy subjects. Similarly, concurrent administration of nateglinide with diclofenac did not alter the pharmacokinetics of diclofenac in these subjects. All treatments were considered to have been both safe and well tolerated.


CONCLUSIONS
These data indicate that concomitant administration of diclofenac with nateglinide does not significantly alter the pharmacokinetic profile of either drug.
Anderson
D M
DM
Ajinomoto Pharmaceuticals Europe Limited, Surrey, United Kingdom.
Shelley
S
S
Crick
N
N
Buraglio
M
M
D000328:Adult; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D003510:Cyclohexanes / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004008:Diclofenac / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions / Q000502:physiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D012016:Reference Values; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D004008:Diclofenac; D000077715:Nateglinide; D010649:Phenylalanine