ABSTRACT
According to a randomized double-blind cross-over design, the short-term (8 weeks, n = 12) and acute (2 h, n = 6) systemic and renal hemodynamic effects of carvedilol (25-50 mg o.d.) and metoprolol (100-200 mg o.d.) were compared in kidney allograft recipients with mild transplant dysfunction and arterial hypertension chronically treated with metoprolol. Cardiac output (Q) was measured by Doppler echography and renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by constant infusion techniques using [123I]iodohippurate and [51Cr]EDTA, respectively. After 8 weeks, mean blood pressure (101 +/- 3 vs. 103 +/- mm Hg) and RBF (318 +/- 14 vs. 316 +/- 14 ml/min) were comparable for the two drugs, whereas heart rate (HR), Q, and GFR (39 +/- 2 vs. 42 +/- 2 ml/min, p < 0.05) were slightly lower and the RBF/Q ratio (6.4 +/- 0.4 vs. 5.8 +/- 0.4%, p < 0.05) was higher with carvedilol than with metoprolol. During short-term treatment, a single dose of metoprolol acutely decreased HR and Q, carvedilol increased RBF, and both carvedilol and metoprolol enhanced the RBF/Q ratio and decreased renal vascular resistance (by 23 and 7%, p < 0.01 carvedilol vs. metoprolol). These data suggest that carvedilol has beneficial acute renal hemodynamic effects in hypertensive kidney allograft recipients with mild transplant dysfunction.
Subject(s)
Adrenergic beta-Antagonists/pharmacology , Carbazoles/pharmacology , Hemodynamics/drug effects , Hypertension, Renal/drug therapy , Kidney Transplantation , Metoprolol/pharmacology , Propanolamines/pharmacology , Adult , Carvedilol , Double-Blind Method , Female , Glomerular Filtration Rate/drug effects , Humans , Male , Middle AgedABSTRACT
A pharmacokinetic study was performed in 13 adult patients with acute nonlymphoblastic leukemia to compare two formulations of 4'-(9-acridinylamino)-methanesulphone-m-ansidide (AMSA): the original formulation, AMSA-NCL, and a water-soluble lyophilized formulation, AMSA-lactate (Bristol Myers, Syracuse, N.Y. USA). Initially, the patients received either AMSA-NCL or AMSA-lactate, 75-90 mg/m2 daily, for 3-7 days as a 1-h infusion. Eight patients subsequently crossed over to receive the other formulation. Plasma samples for drug determination were collected during the first 3 days. A new method for determination of AMSA is described. Acidified plasma samples containing an internal standard were extracted with hexane, then made alkaline, whereafter, AMSA was extracted with ethylacetate. Extracts were reconstituted in absolute ethanol and analyzed by high-pressure liquid chromatography (HPLC) using a reverse-phase C-18 column and UV detection at 254 nm. There were no clear differences in clinical effects and toxicity between the two formulations. Patients with the highest total area under the drug concentration-versus-time curves (AUCs) for plasma concentrations versus time had significantly lower nadir for white blood cell count, suggesting a relation between plasma levels and bone marrow toxicity for AMSA. The pharmacokinetics showed a biphasic elimination for both formulations. The mean terminal elimination half-life of AMSA-NCL and AMSA-lactate was 7.1 and 6.3 h, respectively, and the mean volume of distribution was 105 and 99 L/m2, respectively. No significant differences in the pharmacokinetics comparing days 1 and 3 were seen.(ABSTRACT TRUNCATED AT 250 WORDS)
