Drug dosage in end-stage renal disease (ESRD) patients undergoing haemodialysis. A predictive study based on a microcomputer program.

Drug dosage in end-stage renal disease (ESRD) patients undergoing haemodialysis is a very complex problem because of numerous variables relating to the patient, the type of drug administered and the type of dialysis and dialyser. We carried out a multifactorial study of these parameters using a microcomputer program written in BASIC. Three sets of data were fed into the computer: those relating to the biophysical characteristics of the patient, the type of dialysis and dialyser to be used, and others relating to the chemical and pharmacokinetic characteristics of the drug. From these, a predictive intravenous dosage regimen (bolus and infusion) was compiled for each ESRD patient. To check the program we used 2 drugs (tobramycin and vancomycin) and several types of dialyser. The findings were that, with tobramycin, an ESRD patient should be given different postdialytic doses, depending on the type of dialyser used. The maintenance doses calculated by the program were similar to those usually administered to patients receiving clinical treatment with this drug. In the case of vancomycin, the program calculated the clearance value in vivo through the 'Hemoflow F60' dialyser with a polysulphone membrane. The computer program calculated the maintenance dosage of vancomycin that should be given after each dialysis cycle so that its concentration did not fall below its minimum therapeutic concentration.

Experimental equations to calculate aminoglycoside clearances through cuprophan dialyzers.

Aminoglycosides are a group of antibiotics of particular interest because of their widespread use in the treatment of infections caused by gram-negative bacteria. However, they are difficult to dose accurately because of their narrow therapeutic range and overdosing produces a large number of toxic effects. This paper describes a study carried out with the aim of ensuring the accurate administration of these antibiotics in end-stage renal disease patients undergoing hemodialysis, by developing equations which enable the dosage for individual patients to be calculated according to the dialyzer being used and the operational conditions set up during the dialysis session.

An in vitro study of the influence of a drug's molecular weight on its overall (Clt), diffusive (Cld) and convective (Clc) clearance through dialysers.

The dialyser clearance of a drug is the sum of two components: one diffusive, arising from the concentration gradient across the membrane, and the other convective, arising from the ultrafiltration of plasma water, produced by the increases in hydraulic pressure that the membrane undergoes. To demonstrate the importance of these clearances during haemodialysis, this study analyses the influence of a drug's molecular weight on them. To this end, an experimental study of dialysis in vitro was carried out to determine the clearances, in aqueous solution, of five drugs of increasing molecular weights (theophylline, quinidine, tobramycin, digoxin, and vancomycin), using two series of dialysers with the same type of membrane (Cuprophan), differing in effective surface area and ultrafiltration coefficient. From the data obtained in this study, the importance of quantifying convective clearance during haemodialysis becomes apparent since if it is not taken into account errors of up to 20% and more may be made. This is particularly so if the drug is of high molecular weight and if a high filtration rate is being used.