Abstracts of papers Clinical Pharmacological meeting

s of papers Clinical Pharmacological Meeting Organized by the Dutch Society of Clinical Pharmacology and Biopharmaceutics (Nederlandse Vereniging voor Klinische Farmacologie en Biofarmacie) Utrecht (the Netherlands), 6 October 1989 Organizing committee: Prof. Dr. F.W.H.M. Merkus (Leiden) Prof. Dr. F.W.J. Gribnau (Nijmegen) Dr. Th. Thien (Nijmegen) *Secretary, Laboratory of Pharmacology, Faculty of Medicine, Free University, Van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands. 11-1989 Pharmaceutisch Weekblad Scientific edition K1 COMPARISON OF THE ABSORPTION AND THE DIURETIC EFFECT OF A SINGLE DOSE OF FUROSEMIDE. THE FREE AND THE FIXED COMBINATION OF FUROSEMIDE AND TRIAMTERENE IN HEALTHY MALE ADULTS J.J.M. van Merci I p. Smith 2 F.W.J. Gribnau 1 In order to prevent or to correct hypokalemia caused by diuretics, potassium-sparing agents, such as triarntcrene are frequently co-prescribed. A fixed combination could provide a better patient compliance. In a randomized study in twelve, non-smoking, male volunteers (age 18-22 yr.,weight 59.2-96.1 kg) we compared the absorption anti diurelic effects of 1) furoscmide 40 mg fF), 2) the free combination of F 40 mg and mare• 50 mg (F+T), 3) the fixed combination of F 40 mg and triamterenr 50 mg (FT). The diet on the treatment days contained 150 meq sodium and 100 meq potassium. 24-hours urine was collected in portions after spontaneous voiding for determination of Na, K and Mg. Plasma samples were taken at different points for determination of furosemideand triamterene-plasmalevels. For the statistical analysis two way analysis of variance was used. Results:absorption of furosemide presented as the mean (.• of the AUC,~0 was not different between the three tests (F: 2.58 +. 0.22 I.tg.Wml, F+T: 2.46 +__ 0.20 I.tg.h/ml, FT." 1.97 _.+ 0.t4 l.tg.Wml ). The absorption of triamterene was significantly reduced in FT as compared to F+T (AUC480: F+T: 204.9 + 22.1 lag.h/I, IT: 130.2 _+ 24.5 gg.h/l, p<0.05). There was no difference in excretion rate of furosemide in the three preparations.The same accounted for the excretion rate of triamterene in FT and F+T. The diuretic effect (both sodium excretion and potassium-sparing effect) of FT showed no difference as compared to F+T. Addition of triamterene to F in FT as well as in F+T showed no magnesium sparing effect. Conclusion: 1) Absorption of triamterene, but not of furosemide, was reduced in F'I" as compared to F+T. 2) There was no difference in diuretic effect of FT and F+T. 3) Triamterene did not inhibit the magesiuric effect of furosemide in F+T nor in FT. Dept. of Clin. Pharmacology ~ and Dept. of Internal Medicine z, St. Radboud University Hospital, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. CAFFEINE ATTENUATES DIPYRIDAMOLE-INDUCED SYSTEMIC AND CORONARY VASODILATION IN MAN. P.Smits, W. Aengevaeren, F. Corstens, T. v.d. Werf and Th. Thien. Dipyridamole (DIP) induces vasodilation by an increase of endogenous adenosine levels. Since caffeine (CF) shows adenosine antagonism in-vitro, we investigated whether CF inhibits DIP-induced effects by performing DZP-~~ (Tl)-tests with and without CF. During CF-abstinence ~"'Tl-myocardial imaging was performed after DIP (0.56 mg/kg i.v.). [n l0 patients the DIP~~ were judged as positive, and this group undevwent a 2 "'~ test, but now Z0 min after CF [4 mg/kg i.v.). Afterwards the 20 myocardial 'images were analysed blindly. Results: Baseline plasma CF ranged from 更多