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European Journal of Clinical Pharmacology | 1988

Pharmacokinetics of lisinopril in hypertensive patients with normal and impaired renal function

B. A. M. van Schaik; G. G. Geyskes; P.A. Van Der Wouw; H.H. van Rooij; A. J. Porsius

SummaryThe pharmacokinetics of lisinopril was studied after administration of single and multiple doses of 5 mg to hypertensive patients with normal and impaired renal function.In patients with severe renal failure the peak concentrations were higher, the decline in serum concentration was slower and the time to peak concentration was extended. Accumulation of lisinopril was highly correlated with the creatinine clearance. The effective half-life was doubled and tripled in patients with mild and severe renal impairment, respectively, as compared to patients with a normal renal function. Lisinopril lowered blood pressure in all three groups over 24 h.It is suggested that smaller doses of lisinopril should be administered to patients with severe renal failure.


Inflammation Research | 1990

Adenosine enhances antigen-induced bronchoconstriction and histamine release in rat isolated lungs.

Mark J. Post; J.D. te Biesebeek; J. Wemer; H.H. van Rooij; A. J. Porsius

The effects of adenosine and some of its analogues on bronchoconstriction and mediator release were studied in isolated lungs of actively sensitized rats. Adenosine (ADO) and its analogues R-phenyl-isopropyl-adenosine (R-PIA) and N-ethyl-carboxamide-adenosine (NECA), enhanced antigen-induced bronchoconstriction in a dose-dependent manner. The enhancement of anaphylactic bronchoconstriction by adenosine and its analogues was accompanied by a rise in histamine release. The observed rank order of potency for adenosine and analogues (NECA≥R-PIA>ADO) did not permit an unequivocal classification of the adenosine receptor involved. Dipyridamole and S-(p-nitrobenzyl-6-thioinosine) (NBTI), both inhibitors of adenosine uptake, had no inhibitory influence on the adenosine-induced enhancement of anaphylactic bronchoconstriction. Therefore, this enhancement was likely to be mediated through an extra-cellular receptor. Theophylline inhibited the enhancement of anaphylactic bronchoconstriction by adenosine in a concentration-dependent manner, without affecting preformed mediator release.


Journal of Pharmacological Methods | 1989

In vitro method for measurement of cardiac performance and responses to inotropic drugs after experimentally induced myocardial infarction in the rat

W. Vleeming; P.A. Van Der Wouw; H.H. van Rooij; J. Wemer; A. J. Porsius

In this paper, a method is described for the measurement of the performance of rat hearts with an experimentally induced myocardial infarction of the left ventricle. After ether anesthesia of the animals and left thoracotomy, the left coronary artery was ligated, and the thorax was rapidly closed. The whole procedure took no more than 2 min. Forty-eight hours after the operation, the hearts were prepared for retrograde constant pressure perfusion, according to the Langendorff technique. The effects of the betasympathomimetic drug dobutamine and of the novel phosphodiesterase inhibitor milrinone on the contractile force of the right ventricle and the infarcted left ventricle, as well as on the total coronary flow, were quantified. Sham operated animals were used as control. The maximal obtainable stimulation of the contractility of infarcted hearts by dobutamine was significantly reduced from control. Milrinone increased the contractility in control animals, although to a much lesser extent. This increase was significantly smaller in infarcted hearts. The stimulation of the coronary flow by dobutamine and milrinone was significantly reduced in hearts with an infarction. Milrinone potentiated the effect of isoprenaline significantly. The results of the present study indicate the usefulness and reproducibility of this model for the evaluation of the efficacy of positive inotropic agents on the heart in the presence of a myocardial infarction.


Inflammation Research | 1989

In vivo anaphylaxis in the rat: Effects of phosphodiesterase inhibitors

Mark J. Post; J.D. te Biesebeek; J. Wemer; H.H. van Rooij; A. J. Porsius

On the basis of their inhibitory capacities on the phosphodiesterase enzyme system, we studied the anti-anaphylactic effect of milrinone and sulmazole in comparison with theophylline. For this purpose anaphylactic shock was induced in actively sensitised, spontaneously breathing rats. Milrinone, sulmazole and theophylline reduced anaphylactic bronchoconstriction without affecting the antigen induced fall in blood pressure. Surprisingly, sulmazole reduced mortality significantly.


Biochemical Pharmacology | 1989

Effects of milrinone and salbutamol on antigen induced arachidonic acid metabolism in the isolated rat lung

Mark J. Post; J.D. te Biesebeek; J. Wemer; H.H. van Rooij; F. Zijlstra; M.A. Vermeer; A. J. Porsius

Milrinone and salbutamol inhibit antigen induced stimulated arachidonic acid metabolism, probably at a site before the separation in lipoxygenase and cyclooxygenase pathways


Pulmonary Pharmacology | 1991

Effects of milrinone, sulmazole and theophylline on adenosine enhancement of antigen-induced bronchoconstriction and mediator release in rat isolated lungs

Mark J. Post; J.D. te Biesebeek; J. Wemer; H.H. van Rooij; A. J. Porsius

The effects of adenosine and some of its analogues on bronchoconstriction and mediator release were studied in isolated lungs of actively sensitized rats. The influence of two novel cardiotonic drugs, milrinone and sulmazole on these adenosine-induced effects was compared with that of theophylline, a well known adenosine antagonist. Adenosine (ADO) and its analogues N-ethyl-carboxamide-adenosine (NECA) and R-phenyl-isopropyladenosine (R-PIA), dose-dependently enhanced antigen-induced bronchoconstriction. The enhancement of anaphylactic bronchoconstriction by adenosine and its analogues was accompanied by a rise in histamine release. The rank order of potency for adenosine and analogues with respect to enhancement of anaphylactic bronchoconstriction, was NECA greater than or equal to R-PIA greater than ADO. An unequivocal classification of the adenosine receptor involved, was therefore not possible. Dipyridamole and S-(p-nitrobenzyl-6-thioinosine) (NBTI), both inhibitors of adenosine uptake, had no inhibitory influence on the adenosine-induced enhancement of anaphylactic bronchoconstriction, indicating that this enhancement is mediated by an extra-cellular receptor. Theophylline, milrinone and sulmazole inhibited the enhancement of anaphylactic bronchoconstriction, without affecting preformed mediator release. Theophylline and sulmazole were both more effective as inhibitors of adenosine-enhanced bronchoconstriction than as inhibitors of antigen-induced bronchoconstriction, suggesting adenosine antagonism. Milrinone was equi-effective as inhibitor of both types of bronchoconstriction. Since adenosine antagonism has been associated with the side effects of theophylline it will be interesting to further investigate the therapeutic merits of novel cyclic nucleotide phosphodiesterase inhibitors in the treatment of asthma.


Inflammation Research | 1990

Modulation of histamine release by rat peritoneal mast cells in a superfusion set-up

Mark J. Post; C. Moekoet; J. Wemer; H.H. van Rooij; A. J. Porsius

A new method is presented for studying mediator release in isolated peritoneal cells of the rat. Using a superfusion technique, cells can be maintained in a continuously cleared medium. Cells were stimulated with antigen, compound 48/80 or A23187 to characterize this preparation. In addition, inhibitory effects of theophylline, isoprenaline and cromoglycate on compound 48/80-induced histamine release were studied. We conclude that superfusion is a valid alternative to study mediator release from isolated peritoneal cells.


Cardiovascular Research | 1989

Density of β adrenoceptors in rat heart and lymphocytes 48 hours and 7 days after acute myocardial infarction

W. Vleeming; P.A. Van Der Wouw; J.D. te Biesebeek; H.H. van Rooij; J. Wemer; A. J. Porsius


Journal of Chromatography B: Biomedical Sciences and Applications | 1986

Rapid and simple determination of alprenolol in serum

G.S.M.J.E. Duchateau; W.M. Albers; H.H. van Rooij


Journal of Chromatography B: Biomedical Sciences and Applications | 1989

High-performance liquid chromatographic determination of milrinone in biological tissues and fluids

Ruud Verrijk; H.H. van Rooij; J. Wemer; A. J. Porsius

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F. Zijlstra

Erasmus University Rotterdam

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