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.
It is generally concurred that the effectiveness of extracorporeal dialysis is best evaluated by fractional drug removal, i.e. the proportion of body burden of drug removed during the period of dialysis treatment. Two equations reported in the literature and five equations proposed in this article are examined for their validity in the assessment of fractional drug removal. Potential limitations and applicable conditions of these equations are discussed and compared. Calculations of fractional drug removal are demonstrated using both simulated and experimental data of ethambutol. Depending on the available kinetic measurements during dialysis and post dialysis, one may apply each equation separately or in conjunction with others to the calculation of fractional drug removal.
Dialysis clearance and drug recovery of theophylline were investigated in three peritoneal dialysis patients and the results were compared with those obtained from five hemodialysis patients. Peritoneal clearance averaged 9.5 ml/min, in contrast with the hemodialysis clearance of 84.8 ml/min, indicating a relative inefficiency of peritoneal dialysis with regard to theophylline removal. Theophylline half-life was reduced substantially during hemodialysis, 2.0 to 3.2 hours, in comparison with the normal half-life range of 4.7 to 6.8 hours during peritoneal dialysis. The fraction of theophylline recovered by peritoneal dialysis approximated 3.2 per cent of dose, while hemodialysis recovered up to 40 per cent of the administered dose. The overall observations of half-life, dialysis clearance, and drug recovery suggest a clear advantage of hemodialysis over peritoneal dialysis for theophylline detoxification. However, peritoneal dialysis may be preferred to hemodialysis for uremic patients requiring theophylline therapy. Since the removal of theophylline by peritoneal dialysis is minimal, an undesirable alteration of the theophylline dosage regimen in association with dialysis therapy can thus be avoided.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.