Pharmakokinetik und Dosierung von Dextran 40 in Abh�ngigkeit von der Nierenfunktion

36 Patienten mit unterschiedlicher Nierenfunktion (GFR zwischen 0,5–142 ml/min) erhielten 500 ml 10%iges Dextran 40 (Rheomacrodex®). Dabei ergab sich ein relatives Verteilungsvolumen von 10,2±2,2 1/100 kg. Die Eliminationshalbwertzeiten von Dextran 40 stehen mit der Nierenfunktion (51 Cr-EDTA-Clearance) in einem Zusammenhang, der sich rechnerisch am besten durch eine Potenzfunktion darstellen last. Patienten mit normaler Nierenfunktion (GFR uber 90 ml/min) haben eine Eliminationshalbwertzeit von 573±138 min und eine 12 Std-Recovery im Urin von 48%. Ein Glomerulusfiltrat unter 10 ml/min fuhrt dagegen zur Verlangerung der Halbwertzeit auf das Funffache (Dextran 40-HWZ=2591±1022 min) und zum R…

Accumulation and Adverse Effects of Metoprolol and Propranolol After Concurrent Administration of Cimetidine

Pharmacokinetics of metoprolol, propranolol and atenolol were investigated in six healthy volunteers following 7 days of oral monotherapy with these drugs and after 7 days concurrent administration of each of these betareceptor antagonists with cimetidine. Application of cimetidine did not lead to any interaction with atenolol, whereas mean peak plasma levels of metoprolol were increased by 70%, and those of propranolol by 95% due to concurrent administration of cimetidine (p < 0.05). The AUC of the two last mentioned beta blockers behaved similarly (p < 0.05). Measurement of exercise-induced tachycardia on the 6th day of administration showed no differences between monotherapy with the bet…

Pharmacokinetics of atenolol in relation to renal function

The plasma levels and urinary excretion of carteolol and its main metabolites 8-hydroxycarteolol and carteolol glucuronide were investigated in 6 healthy subjects and 9 patients with varying degrees of renal impairment following a single oral dose of 30 mg carteolol hydrochloride. In healthy subjects the half-life of carteolol was 7.1 h. 63% of the administered dose was recovered unchanged in urine, and in all 84% was excreted by the kidneys. The renal clearance of carteolol was 255 ml/min. In chronic renal failure (CRF) the terminal half-life was increased to a maximum of 41 h. Both the elimination rate constant and renal clearance were closely related to the creatinine clearance. In CRF t…

Clinical pharmacokinetics of atenolol — A review

Atenolol is a hydrophilic betareceptor blocking drug, which is predominantly eliminated via the kidneys, only about 5% of the atenolol is metabolised by the liver. After oral administration atenolol is incompletely absorbed from the intestine, so about 50% of the beta blocker are finally biovailable. In plasma only 3% of atenolol are protein-bound. There exists a linear relationship between the atenolol plasma levels and the degree of beta blocking effect measured by inhibition of the exercise-induced tachycardia. No correlation was found between plasma levels of atenolol and blood pressure lowering activity of the drug. After oral administration elimination half life of atenolol is calcula…

Interaction of atenolol with furosemide and calcium and aluminum salts

Six healthy subjects were treated with 100 mg atenolol. After a therapy-free interval of 4 wk the same subjects received the same dose of atenolol with furosemide, 40 mg, with calcium (as the lactate gluconate and carbonate), 500 mg, or with aluminum hydroxide, 5.6 gm. Atenolol alone and in combination was administered first as a single oral dose; a long-term 6-day treatment began 48 hr later. Addition of furosemide did not influence atenolol kinetics, but aluminum hydroxide led to an insignificant reduction (P greater than 0.05) of mean peak plasma levels of about 20% and of the area under the plasma concentration-time curve (AUC -infinity) from 5818 to 4353 ng ml-1 hr (P greater than 0.05…

Dosierung und Elimination von Dextran 40 bei H�modialysepatienten

Bei 24 Hamodialysepatienten wurden nach einmaliger und wiederholter Gabe von Dextran 40 (Rheomacrodex®) die Dextranspiegel im Serum bestimmt und daraus die Eliminationshalbwertzeiten errechnet. Diese betrugen bei Heimdialysepatienten 2237±447 min, bei Zentrumsdialysepatienten 4283±810 min und waren damit gegenuber nierengesunden Patienten (HWZ=573±183 min) auf das Funf- bzw. Zehnfache verlangert. Die Unterschiede zwischen Heimdialyse- und Zentrumsdialysepatienten erklaren sich durch die bessere Nierenrestfunktion der ersteren. Wahrend der Hamodialyse kam es zu keinem Abfall der Dextranspiegel i.S. Weiterhin zeigte sich, das die exponentielle Elimination von Dextran 40 uber einen Beobachtung…

Retarded Elimination of a High-Molecular Enzyme-Substrate-Complex after Hydroxyethyl-Starch-Infusion

During a pharmacokinetic study with hydroxyethyl starch we found, that this plasma substitute induces a regular increase of serum amylase. In 54 patients after infusion of 500 ml 6% hydroxyethyl starch (HES) an increase of serum amylase was observed, which in 51 cases exceeded the upper limit of normal (190 U/l). In most cases serum amylase reached values twice as high as the basal value. Renal function influenced duration of increased serum amylase values, but did not influence maximum increases (201 ±15 U/l; mean ± SEM). In patients with advanced renal failure (GFR = 2–10 ml/min) serum amylase was still markedly elevated after 72 hours (298 ± U/l; mean ± SEM). In patients with normal rena…

Single Intravenous Dose Kinetics and Accumulation of Atenolol in Patients with Impaired Renal Function and on Hemodialysis

The concentration of atenolol in plasma and urine was determined following an intravenous (i.v.) dose given to 17 hypertensive patients with a glomerular filtration rate (GFR) between 5 and 105 ml/min and in 4 patients on hemodialysis. In patients with normal renal function the mean half life of elimination was calculated to be 6.8 h. This value increased to a mean of 50.1 h in patients with a GFR below 10 ml/min. In patients on hemodialysis the half life of elimination was about 4 h. The elimination rate constants as well as the body and renal clearances of atenolol have a significant correlation with the GFR. Although accumulation of atenolol was observed, especially after multiple oral d…

Atenolol interaction with aspirin, allopurinol, and ampicillin.

Atenolol kinetics were investigated in six healthy subjects after 100 mg orally, as monotherapy a 6-day treatment began 48 hr later. After a therapy-free interval of 4 wk, the same subjects received the same dose of atenolol with 1 gm ampicillin, 500 mg aspirin, and with 300 mg allopurinol. Allopurinol and aspirin did not substantially alter the kinetics of atenolol. After a single oral dose of 100 mg atenolol combined with 1 gm ampicillin, the bioavailability of atenolol was reduced to 36 +/- 5% compared to 60 +/- 8% after monotherapy. During long-term treatment with atenolol and ampicillin the bioavailability of atenolol fell to 24% (P less than 0.01). Mean peak plasma levels were lowered…

Elimination of hexamethylene diisocyanate cross-linked polypeptides in patients with normal or impaired renal function

Infusions of 3.5% isocyanate cross-linked polypeptide solution 500 ml were given to 52 patients with normal or impaired renal function: glomerular filtration rate (GFR)=0–133 ml/min. The serum concentration and urinary excretion of hydroxyproline were measured and the equivalent polypeptide concentrations were calculated from the results. In patients with normal renal function (GFR>90 ml/min) the proportion of polypeptide excreted in the urine up to 12 h was 45.4±2.6% ( $$\bar X$$ ±SEM), up to 24 h 47.7±2.9% and up to 48 h 49.3±3.4%. In patients with moderate renal insufficiency (GFR=30–90 ml/min) there was no decrease in polypeptide excretion and even in patients with more serious impairme…

Die Pharmakokinetik von harnstoffvernetzter „Gelatine“ bei Patienten mit normaler und eingeschränkter Nierenfunktion

Kolloidale Plasmaersatzmittel (kPEM) auf Gelatine-Basis werden normalerweise vorwiegend uber die Nieren augeschieden [1,6,91. 5–17% werden intestinal eliminiert, wie sich im Tierexperiment zeigen lies [9]. Ein geringer Prozentsatz wird auserdem metabolisiert, wobei sich ca. 3% radioaktiv markierter Gelatine 2 Std nach Applikation in der Ausatmungsluft nachweisen lassen. Als abbauende Enzyme kommen hierbei vorwiegend Trypsin, Kathepsin und Plasmin in Frage [5]. Aufgrund dieser uberwiegend renalen Elimination stellt sich die Frage, ob und bei welchem Grad der Niereninsuffizienz die Gesamtelimination der Gelatine verzogert ist und eine Kumulation auftritt.

Macroamylasaemia after treatment with hydroxyethyl starch

After infusion of 500 ml of 6% hydroxyethyl starch into fifty-four patients an increase of serum amylase was observed which in fifty-one cases exceeded the upper limit of normal (190 U/l). In most cases serum amylase reached twice the basal value. Renal function influenced the duration of the increase in serum amylase, but not the maximum increase (201+/-15 U/l; mean+/-SEM). In patients with advanced renal failure (glomerular filtration rate (GFR) = 2-10 ml/min) serum amylase was still markedly elevated after 72 h (298+/-24 U/l; mean+/-SEM). In patients with normal renal function (GFR greater than 90 ml/min) serum amylase decreased to 183+/-40 U/l (mean+/-SEM) within 72 h without reaching b…

Interaction of cimetidine with metoprolol, propranolol, or atenolol.