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.

High performance liquid chromatography determination of doxorubicin and daunorubicin in plasma using UV detection and column switching.

A method for the determination of doxorubicin and daunorubicin in plasma is described. The plasma is injected directly into a loop column and then washed with water. After switching the injection valve, the sample is separated on a phenyl column using detection at 254 nm. The detection limit is 10 ng/mL, the coefficient of variation is 7% for 100 ng/mL of doxorubicin and 4% for 200 ng/mL of daunorubicin.

Effect of renal impairment on distribution of ofloxacin.

A study was made of the plasma and distribution kinetics of ofloxacin administered at a dosage of 400 mg orally to a group of healthy volunteers and a group of patients with renal impairment. Blood and blister fluid samples were taken at programmed times from all individuals included in the study. The analytical techniques for the determination of ofloxacin in both fluids were a plate diffusion method and a high-performance liquid chromatographic technique. The fitting of the experimental data to the kinetic model used was done with the help of the AUTOAN 2 and NONLIN 84 computer programs. In the groups of healthy volunteers, the elimination half-life mean values were found to be 5.1 and 5.9 h in plasma and blister fluid, respectively. The maximum concentration reached in plasma (3.9 micrograms/ml) proved to be slightly higher than that in interstitial tissue fluid (2.8 micrograms/ml). In the patients with renal impairment, the maximum concentrations in both plasma and blister fluid were significantly increased, in the order of 5 to 8 micrograms/ml in the former and 3 to 4 micrograms/ml in interstitial tissue fluid. The parameters seen to undergo an increase as a result of the renal impairment were the area under the curve of the plasma-time levels, the area under the curve of the blister fluid-time levels, and the elimination half-life in plasma and blister fluid. The degree of absorption and the access capacity of the drug to interstitial tissue fluid remained constant.