Sergio R. Acchiardo

Clinical efficacy, safety, and pharmacokinetics of indapamide in renal impairment

The efficacy and safety of a new diuretic-antihypertensive drug, indapamide (2.5 mg/day), were evaluated in hypertensive patients with normal renal function, in patients with various degrees of chronic renal failure, and in hypertensive patients undergoing long-term maintenance hemodialysis. The results obtained from single-blind, placebo-controlled studies indicate that indapamide is a safe and effective agent to use in lowering the blood pressure of hypertensive patients with normal renal function, those with various degrees of renal impairment, and those who are undergoing long-term maintenance hemodialysis. No significant side or toxic effects were noted in these studies. Furthermore, indapamide does not accumulate in the bloodstream of patients with renal impairment and is not dialyzable.

Folie acid dosage for chronic hemodialysis patients

The doses of folic acid, neeessary to avoid folic acid deficiency in patients being maintained on hemodialysis, have been estimated to be between land 5 mg daily. To more precisely define an adequate dose of folic acid, 6 anephric patients were studied. The patients were maintained on hemodialysis and received, in a crossover fashion, 1 mg and 5 mg of folic acid for 3 wk. In a second crossover study, 3 anephric patients were first maintained on 0 and then on 1 mg of folic acid after each dialysis for 3‐wk periods. Pre‐ and postdialysis folic acid blood levels were measured and dialyzer clearances of folic acid were determined. The results of this study support the conclusion of the Food and Drug Administration report suggesting that daily doses of 1 mg of folic acid are adequate to sustain therapeutic folate levels. The data further indicate that the administration of 1 mg of folic acid after each dialysis, rather than 1 mg of folic acid daily, can provide adequate folate.

Fluoride kinetics after enflurane anesthesia in healthy and anephric patients and in patients with poor renal function

Enflurane, a fluorinated methylethyl ether, is metabolized, in part, to inorganic fluoride, Methoxyflurane has similar metabolism, and cases of fluoride ion‐induced renal failure have been reported after its use. This prospective study was initiated to determine fluoride ion kinetics after enjiurane anesthesia in 16 healthy patients, 18 anephric patients, and 6 patients each having a creatinine clearance of less than 5 ml/min (on dialysis). Serum and urine inorganic fluoride levels were determined. There was no clinical or statistical significance difference among the 3 groups with respect to maximum inorganic fluoride ion concentration or the time to reach it. The fluoride ion values were never above the 50 µM level that has been reported to cause subclinical renal toxicity. The fluoride ion concentration in serum fell rapidly after termination of anesthesia even in the anephric patients. This is presumed to be due to uptake of the ion by bone. Patients with low creatinine clearance also have low fluoride ion clearance. Statistical but not clinical significance was found in the comparison between pre‐enflurane and the 24‐hr fluoride ion va lues in the anephric and low creatinine clearance patients, but this did not persist after one dialysis.

The comparative bioavailability of liquid, wax-matrix, and microencapsulated preparations of potassium chloride

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Ultrastructural changes in gentamicin nephrotoxicity

Although described in laboratory animals, the ultrastructural changes in the kidneys of humans with gentamicin-induced acute renal failure have not been well documented. This report details the clinical and pathologic features of a patient with gentamicin-induced nephrotoxicity with special emphasis on the electron microscopic findings.

Liquid and solid potassium chloride: bioavailability and safety.

Studies have suggested that microencapsulated preparations of potassium chloride may pose less risk to the upper gastrointestinal mucosa than the currently available wax‐matrix preparations. Based on our own clinical experience and data available from the literature, we have concluded that (1) liquid and slow‐release preparations of potassium chloride are safe and effective when used appropriately and (2) at present there is no conclusive evidence to suggest that lesions of the upper gastrointestinal tract are more prevalent with one slow‐release preparation than with another.

Fluoxymesterone therapy in anemia of patients on maintenance hemodialysis: comparison between patients with kidneys and anephric patients.

Nineteen patients with their kidneys and 11 anephric patients who were stable on maintenance hemodialysis received 20 mg a day of Fluoxymesterone. At the end of four months, there was a significant increase (p less than 0.005) in the mean hematocrit with a parallel increase in the hemoglobin level in both groups of patients. Concomitantly, we observed an increment of the red cell mass that was significant at the level of p less than 0.05. Blood transfusion requirements decreased significantly (p less than 0.1), independent of the presence or absence of kidneys. No changes in body weight, serum albumin, and serum cholesterol levels were observed. Secondary effects were hirsutism and hoarsening of the voice.

The pharmacokinetics of trichlormethiazide in hypertensive patients with normal and compromised renal function

SummaryThe pharmacokinetics of trichlormethiazide (TCZ) was studied in twelve patients after a single 4 mg dose. Seven patients had normal renal function with creatinine clearances greater than 90 ml/min. Five patients had compromised renal function with creatinine clearances averaging 48±29 ml/min. The TCZ plasma half life and area under the plasma concentration-time curve (AUC) were significantly greater in patients with impaired function, compared to patients with normal renal function. There were no significant differences between the two patient groups in terms of either rate of drug absorption or total urinary recovery of unchanged drug. Furthermore, there was no correlation between peak drug levels or AUC and renal excretion of water or electrolytes.

What Will Be the Impact of Erythropoietin on Chronic Dialysis

found depending upon the time of study. Most investigators used the 4 to 6 month time frame for the repeat studies, and found a rise in peripheral resistance and a drop in cardiac output in response to the normalization of the hematocrit (4). They theorized, therefore, that the hypertension was merely a reflection of the increased peripheral resistance. Our studies (5 ) , on the other hand, demonstrated that the nature of the hemodynamic response to the elimination of the anemia changed over time and differed from that seen with transfusion therapy. While we also observed the rise in total resistance at 6 months and 1 year, the early hemodynamic response was more cardiogenic, with cardiac output increasing and peripheral resistance decreasing (Table 1). Differences in the hemodynamic responses among the patients who became hypertensive, and those

Implications for the Role of Endogenous Nitric Oxide Inhibitors in Hemodialysis Hypotension

Hypotensive episodes during hemodialysis in patients with end-stage renal disease in the absence of inadequate maintenance of the plasma volume, preexistence of cardiovascular disease, or autonomic nervous system dysfunction is accompanied by increase in the plasma concentrations of the end-products of nitric oxide metabolism, above the levels expected based on the reduction of urea. Factors that can influence the synthesis of nitric oxide or the regulation of the effects of this free radical in patients with chronic renal failure are reviewed. Convergence of these factors and their interactions during the hemodialysis procedure are discussed as the basis for the generation of excessive amounts of nitric oxide that serves as an important contributing factor in the development of symptomatic hypotension.