Summary
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.
References
Berman M, Beltz WF, Greif PC, Chabay R, Boston RC (1983) Consam user's guide. Laboratory of Mathematical Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD
Brater DC (1986) Drug-drug and drug-disease interactions with nonsteroidal antiinflammatory drugs. Am J Med 80 [Suppl 1A]: 62–77
Brozović M, Mackie I (1991) Investigation of bleeding tendency. In: Dacie JD, Lewis SM (eds) Practical haematology. Livingstone, London, pp. 293–318
Cremer KF, Pieper JA, Joyal M, Mehta J (1984) Effects of diltiazem, dipyridamole, and their combination on hemostasis. Clin Pharmacol Ther 36: 641–644
Dale J, Landmark KH, Myrhe E (1983) The effects of nifedipine, a calcium antagonist, on platelet function. Am Heart J 105: 103–105
Jones CR, Pasanisi F, Elliott HL, et al. (1985) Effects of verapamil and nisoldipine on human platelets: in vivo and in vitro studies. Br J Clin Pharmacol 20: 191–196
Murphy MB, Orchard MA, Conway EL, Barrow SE (1985) The effects of nifedipine on platelet aggregation and plasma 6-keo-PGF1α, and its interaction with indomethacin. Eur J Clin Pharmacol 29: 413–416
Ring ME, Martin GV, Fenster PE (1986) Clinically significant anti-platelet effects of calcium-channel blockers. J Clin Pharmacol 26: 719–720
Schran HF, Jaffe JM, Gonasun LM (1988) Clinical pharmacokinetics of isradipine. Am J Med 84 [Suppl. 3B]: 80–89
Sinzinger H, Virgolini I, Rauscha P, O'Grady JO (1992) Isradipine improves platelet function in hypertensive. Eur J Clin Pharmacol 42: 43–46
Todd PA, Sorkin EM (1988) Diclofenac sodium: a reappraisal of its pharmacodynamics and pharmacokinetic properties, and therapeutic efficacy. Drugs 25: 244–285
Verbeeck RK (1990) Pharmacokinetic drug interactions with nonsteroidal antiinflammatory drugs. Clin Pharmacokinet 19: 44–66
Weiss K, Fitscha P, O'Grady J, Sinzinger H (1989) Isradipine: a potent calcium blocker with beneficial effects on platelet function and vascular prostacyclin production. Thromb Res 54: 311–317
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
De Sommers, K., Kovarik, J.M., Meyer, E.C. et al. Effects of diclofenac on isradipine pharmacokinetics and platelet aggregation in volunteers. Eur J Clin Pharmacol 44, 391–393 (1993). https://doi.org/10.1007/BF00316480
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00316480