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Biomedical subjects

W Sziegoleit

Publications and source records attributed to W Sziegoleit.

At least 19 recordsLinked to original sources
PubMed2000

Relationship between mycophenolate mofetil side effects and mycophenolic acid plasma trough levels in renal transplant patients

There has been limited experience with routine therapeutic monitoring of mycophenolic acid (MPA; CAS 24280-93-1), which is the active metabolite of the new immunosuppressive prodrug mycophenolate mofetil (MMF; CAS 115007-34-6). MMF was introduced with recommendation for fixed oral dosing (1 g twice daily) in combination with cyclosporin A (CSA) and a glucocorticoid for the prevention of renal allograft rejection. In the course of routine CSA monitoring a MPA monitoring was performed in adult renal transplant patients receiving MMF in combination with CSA and methylprednisolone (MEP). For 30 consecutive patients with 234 plasma samples the relationship of MMF doses used and MPA plasma through levels estimated at steady state (C88 min) to clinical outcome was evaluated retrospectively. The MPA concentrations were determined with the enzyme-multiplied immunoassay technique (EMIT mycophenolic acid assay) on a Cobas Mira Plus analyzer. The within-run (n = 10) and between-run (n = 10) coefficients of variation were 3.6%, 3.5%, 3.1% and 3.6%, 5.1%, 6.7% analysing three MPA level plasma controls (1.25 mg/l, 7.5 mg/l, 12.5 mg/l), respectively. The data analysis of the MPA plasma trough levels resulted in a high variability between patients (0.3 to 3.4 mg/l) received the recommended fixed MMF dose (2 g/day). There was a higher incidence of adverse reactions with increasing MPA plasma trough levels (2.13 +/- 1.35 mg/l in 13 patients with side effects versus 1.53 +/- 0.67 mg/l in 17 patients without side effects; p < 0.001), regardless of reduction of MMF dose (1.77 +/- 0.3 g/day versus 1.89 +/- 0.2 g/day; NS), respectively. No acute rejection episodes occured under MMF administration in combination with CSA and MEP. The study shows that the to date recommended MMF dose resulted in individual, quite different MPA plasma trough levels, which were associated with incidence of side effects rather than the MMF doses. Therefore, monitoring of plasma MPA trough levels and individual dose adjustment could be helpful to reduce the incidence of adverse reactions and to increase the safety of MMF therapy.

Journal Article↗
PubMed1999

Drug interaction between mycophenolate mofetil and tacrolimus detectable within therapeutic mycophenolic acid monitoring in renal transplant patients.

The possible pharmacokinetic interaction between the new immunosuppressive mycophenolate mofetil (MMF) and tacrolimus (TAC), respectively, was assessed by comparing routinely estimated mycophenolic acid (MPA) plasma trough levels of 15 consecutive renal transplant patients receiving MMF in combination with methylprednisolone (MEP) and cyclosporin A (CSA, 10 patients) or in combination with MEP and tacrolimus (TAC, 5 patients). Coadministration of TAC instead of CSA resulted in a significant increase of mean MPA plasma trough levels [3.4 +/- 1.3 microg/mL (n = 22) versus 1.87 +/- 1.1 microg/mL (n = 57); p < 0.001], despite lower MMF doses [1.5 +/- 0.5 g/d versus 1.7 +/- 0.3 g/d (not statistically significant)]. This elevation in MPA levels is possibly caused by an interaction between MMF and TAC and could lead to a recommendation to monitor MPA plasma levels with appropriate dose adjustment.

Adult↗
PubMed1991

[Serum thromboxane B2 and prostaglandin F2 alpha in familial combined hyperlipoproteinemia and familial hypercholesterolemia].

In continuation of investigations on primary hyperlipidaemias, we determined serum thromboxane (TX) B2 and prostaglandin (PG) F2 alpha after standardized blood clotting in patients without hyperlipidaemia and without (group 1, n = 11) or with coronary heart disease (CHD; group 2, n = 5), in patients with familial combined hyperlipoproteinaemia and without (group 3, n = 4) or with CHD (group 4, n = 5), as well as in patients with familial hypercholesterolaemia and CHD (group 5, n = 5). TXB2 was detected by gas chromatography and PGF2 alpha by means of radioimmunoassay. The TXB2 level did not differ significantly between the groups, but there was a tendency to higher values in hyperlipidaemia, while in group 5 the level tended to decrease with rising serum LDL-cholesterol and in group 3 it tended to increase with rising serum apolipoprotein B. The PGF2 alpha level was significantly lower in group 4 than in groups 1 and 3. It showed in group 5 a negative correlation with serum LDL-cholesterol and in group 3 a positive correlation with serum triglycerides.

Adult↗
PubMed1991

Verapamil and the synthesis of prostacyclin in human veins.

The synthesis of the vasodilator prostacyclin (PGI2) depends on the intracellular calcium concentration. For this reason the purpose of this study was to document the effects of verapamil (1), a slow calcium channel blocking agent on venous tissue. Human varicose veins were studied which were removed by a stripping operation. The veins were investigated ex vivo and in vitro. For ex vivo studies 11 patients were given 0.01 g 1 i.v. during the operation. In vitro experiments were carried out by an addition of 22 mumol/l 1 to the incubate. The synthesis of PGI2 was studied according to the inhibition of the ADP induced platelet aggregation without and with addition of substrate (prostaglandin endoperoxide H2). 1 did not induce changes in the synthesis of PGI2, neither after administration to patients nor after addition to the incubation fluid compared to control vessels without addition of 1.

Adenosine Diphosphate↗
PubMed1990

[The effect of dipyridamole on the results of allogenic kidney transplantation].

In a prospective randomized trial the anti-thrombotic effect of dipyridamole was studied in 64 patients after cadaveric kidney allotransplantation. The frequency of early graft function was significantly higher in the control group, whereas the incidence of arterial and venous thromboses were not different. One-year graft survival could not be improved by dipyridamole. Therefore, dipyridamole should not be recommended in cadaveric kidney allotransplantation.

Cadaver↗
PubMed1989

Bioavailability of trapidil tablets.

Trapidil was given orally (200 mg, Rocornal dragees 100 mg) and intravenously (100 mg) to 12 healthy volunteers. Serum samples were analyzed for trapidil by HPLC. Complete bioavailability was obtained and a mean absorption time of 66.4 min was calculated using the method of curve moments.

Administration, Oral↗
PubMed1988

Cardiac and side effects of prostaglandin F2 alpha in patients with extrasystoles.

In 17 patients with cardiac extrasystoles, prostaglandin (PG) F2a (= alpha) administered intravenously at consecutive infusion rates of 25 to 100 micrograms/min showed the following effects in a dose-dependent manner: prolongation of total electromechanical systole, pre-ejection period, and left ventricular ejection time, indicating a negative inotropic activity, increase in systolic and diastolic blood pressure, and incidence of side effects. An additional 2 patients were excluded from the uniform evaluation because the PGF2a dosage was changed owing to a clear antiarrhythmic action in one and serious side effects in the other. The results supplement clinical-pharmacological findings with PGF2a.

Anti-Arrhythmia Agents↗
PubMed1988

Influence of pentoxifylline administered in vivo on the synthesis of PGI2 in human varicose veins.

The influence of pentoxifylline on the synthesis of prostacyclin (PGI2) was studied using human varicose veins removed by a stripping operation. Patients got 100 mg pentoxifylline iv. during the operation. The synthesis of PGI2 was studied according to the inhibition of the ADP-induced platelet aggregation without and with addition of substrate (100 ng prostaglandinendoperoxide H2) to the incubation fluid. There were no changes in the synthesis of PGI2 compared to control values.

Epoprostenol↗
PubMed1987

Trapidil does not affect serum levels and cardiotonic action of digoxin in healthy humans.

The influence of trapidil on serum levels and cardiac effects of digoxin was investigated in 10 healthy men, intraindividually compared with placebo. Each subject took digoxin orally for 9 days (0.375 mg daily on days 1 to 8, 0.25 mg on day 9) either combined with trapidil (400 mg daily on days 1 to 8, 200 mg on day 9) or combined with placebo in a cross-over design. Trapidil failed to change significantly the steady-state serum digoxin concentrations on day 9 of treatment. It did also not alter significantly the following digoxin effects: shortening in QS2c time indicating the cardiotonic digoxin effect, shortening in QTc time, increase in PTQ index. But trapidil prevented the negative chronotropic digoxin effect.

Adult↗
PubMed1986

Influence of a cod liver oil diet in healthy and insulin-dependent diabetic volunteers on fatty acid pattern, inhibition of prostacyclin formation by low density lipoprotein (LDL) and platelet thromboxane.

Ten healthy and twenty diabetic volunteers (type 1) received 15 capsules (à 450 mg) cod liver oil for 2 weeks daily in addition to a "normal" diet. The levels of eicosapentaenoic acid in the plasma phospholipids of both groups were increased after the treatment. The inhibition of the prostacyclin formation by LDL was diminished when the LDL was isolated after the treatment in comparison to LDL taken in the same concentration and from the same donors before it. The thromboxane B2 (TXB2) synthesis capacity of clotting whole blood, thrombin-induced TXB2 formation by platelets as well as the 15(S)-hydroxy-11 alpha,9 alpha-epoxymethano-5Z, 13E-prostadienoic acid-induced platelet aggregation were not altered by the treatment in healthy volunteers, whereas in diabetics the TXB2 formation capacity of clotting whole blood was decreased after the treatment in comparison with before it.

Adult↗
PubMed1986

[Effect of iloprost on aggregation behavior in kidney conditioning and changes in iloprost concentration in kidney preservation].

The conditioning of the donor by 1.0 microgram/kg X min Iloprost over 15 minutes leads to a considerable inhibition of the aggregation of thrombocytes in the domestic pig. 160% more ADP had to be added than before the application of Iloprost. When 0.5 microgram/ml Iloprost are added to the perfusion fluid and to the reperfusion fluid 0.22 microgram/ml and 0.27 microgram/ml, respectively, are to be proved in the venous efflux. Whether or not the difference is absorbed or metabolized must remain open. During the 72-hour storage of the kidney in a Euro-Collins-solution with 0.5 microgram/ml Iloprost after 24 hours a decrease of 0.34 microgram/ml, after 48 hours to 0.33 microgram/ml and after 72 hours to 0.20 microgram/ml takes place. Thus Iloprost is present in an effective concentration also after 72 hours. The decrease to one plateau rather speaks for a consumption by active metabolic effect or absorption than for a chemical decomposition.

Animals↗
PubMed1986

Are serum levels and cardiac effects of digoxin influenced by indometacin?

Intraindividually compared to placebo, the possible influence of an oral pretreatment with the cyclooxygenase inhibitor indometacin on serum concentrations and cardiac effects of digoxin, administered by a controlled intravenous infusion, was evaluated in 6 healthy male humans. A significant pharmacokinetic or pharmacodynamic interaction between both drugs could not be found. Indometacin only tended to elevate serum digoxin levels, to strengthen the digoxin induced decrease in the electrocardiogram parameters heart rate and QTc time as well as to reduce the positive inotropic action of digoxin measured by systolic time intervals and PTQ index.

Adult↗
PubMed1984

Influence of indometacin and acetylsalicylic acid on the therapeutic effectiveness of talinolol in patients with essential hypertension.

Clinical-pharmacological investigations on interactions between cyclo-oxygenase inhibitors and beta-adrenoceptor blocking agents continuing, indometacin and acetylsalicylic acid (ASA) were added to a monotherapy of talinolol in two groups of hypertensive outpatients. Both added drugs reduced slightly the blood pressure lowering effect of talinolol, but did not alter its negative chronotropic effect. Indometacin abolished a talinolol-induced increase in serum triglycerides and caused a small decrease in serum cholesterol. ASA diminished slightly blood glucose. Probably the observed interactions and side effects are not important practically.

Adrenergic beta-Antagonists↗