Drug Therapy in Patients Undergoing Haemodialysis

Abstract

Haemodialysis is utilised therapeutically as supportive treatment for end-stage renal disease (ESRD). In conjunction with haemodialysis therapy, ESRD patients frequently receive a large number of drugs to treat a multitude of intercurrent conditions. Because of the impaired renal function in ESRD patients, dosage reduction is often recommended to avoid adverse drug reactions, particularly for drugs and active metabolites with extensive renal excretion. On the other hand, if the removal of a drug by haemodialysis during concomitant drug therapy is significant, a dosage supplement would be required to ensure adequate therapeutic efficacy. Knowledge of the impact of haemodialysis on the elimination of specific drugs is therefore essential to the rational design of the dosage regimen in patients undergoing haemodialysis. This review addresses the clinical pharmacokinetic aspects of drug therapy in haemodialysis patients and considers: (a) the effects of ESRD on the general pharmacokinetics of drugs; (b) dialysis clearance and its impact on drug and metabolite elimination; (c) the definition of dialysability and the criteria for evaluation of drug dialysability; (d) pharmacokinetic parameters which are useful in the prediction of drug dialysability; and (e) the application of pharmacokinetic principles to the adjustment of dosage regimens in haemodialysis patients. Finally, drugs commonly associated with haemodialysis therapy are tabulated with updated pharmacokinetics and dialysability information.

Pharmacokinetics of carumonam (AMA-1080) in patients with impaired renal function and in those undergoing hemodialysis

“…The widely recommended modification of the dose schedule when renal function is reduced is to prolong the dosage interval, multiplying it by ,n/,Bf, with 1n and Brf being the ,B values in normal subjects and those with renal failure, respectively (2). By using the data obtained in the present study, it is predicted that the steady-state maximum and minimum serum carumonam levels would be 93.1 and (10). In the present study, equations 1, 3, and 5 yielded similar values, while, although not statistically significant, equations 2 and 4 yielded somewhat lower clearance values.…”

Prediction of Pharmacokinetics of Antibiotics in Patients with End-Stage Renal Disease

“…1,2) Although the distribution volumes of most drugs rise slightly because of water retention, these discrepancies were considerably smaller than the total volume of body fluid and as a result the influence of the pharmacokinetics would be limited. 4) A difference was also found in the protein binding due to the reduction of net protein content and accumulation of various kinds of uremic toxins in ESRD patients.…”

“…In contrast, hemodialysis sometimes results in an inadequate decrease of the plasma drug level from the therapeutic range. [1][2][3][4] Consequently, pharmacokinetic information for ESRD patients is requisite in the process of new drug development in order to ascertain the effect of renal failure on tolerability and exposure and to determine the dosage regimen. 5) However, the clinical study of ESRD patients has not often been performed due to difficulties with patient enrollment.…”

Ibuprofen kinetics in patients with renal insufficiency who are receiving maintenance hemodialysis

“…Dialysis-dependent patients with renal failure actually spend a small fraction (< 10%) of their time undergoing dialysis, and it is not necessarily true that the observed alterations in ibuprofen kinetics would apply to the inter-dialysis interval. Removal of ibuprofen by the dialysis procedure appears to be minimal (20), suggesting that dialysis itself probably does not importantly enhance clearapce of free drug. Renal insufficiency and/or concurrent medications can be associated with reduced clearance of drugs whose major route of clearance is hepatic biotransformation, whether or not drug clearance is measured during dialysis itself (21)(22)(23)(24).…”