Effects of diclofenac on isradipine pharmacokinetics and platelet aggregation in volunteers.
In this open, two-period crossover study in 18 healthy male volunteers, a single oral dose of 50 mg diclofenac was administered alone and on day 7 of multiple oral dosing of 5 mg b.i.d. isradipine to assess a possible pharmacokinetic interaction. The effect of these drugs on ex vivo platelet function was also determined. Serial blood samples were obtained over 12-hour periods on three occasions: after the single diclofenac dose; after the morning dose of isradipine on day 6 and after co-administration of both drugs on day 7 of steady-state isradipine administration. Additional samples were taken at 2 h post dose for determination of ex vivo platelet aggregation. Isradipine plasma concentrations were determined by a gas chromatographic method and diclofenac plasma concentrations by an HPLC method. The pharmacokinetic characteristics of diclofenac were unaltered during co-administration. The maximum plasma concentration of isradipine was increased 19.6% during co-administration from 5.06 to 6.05 ng.ml-1. This is not expected to be of clinical importance. Isradipine's apparent total body clearance and steady-state AUC remained unchanged. Ex vivo induced platelet aggregation was not affected by any of the treatments.
Department of Pharmacology, University of Pretoria, South Africa.
D K
DK
Sommers
J M
JM
Kovarik
E C
EC
Meyer
M
M
van Wyk
J R
JR
Snyman
M
M
Blom
S
S
Ott
P
P
Grass
K
K
Kutz
D000328:Adult; D000704:Analysis of Variance; D004008:Diclofenac / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D017275:Isradipine / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D012016:Reference Values
D004008:Diclofenac; D017275:Isradipine