Pharmacokinetics of Newer Drugs in Patients with Renal Impairment (Part I)

Abstract

Many drugs are eliminated via the renal route and the usual dose must be modified in patients with severe renal impairment. This review is an attempt to supply physicians with the more recent data on pharmacokinetic studies of new drugs administered in uraemic patients. The review is in 2 parts: the first indicates the results of studies on the pharmacokinetics of antibiotic agents, antifungal, antiviral and antiulcer drugs, and nonsteroidal anti-inflammatory drugs. Special mention is made of epoetin (recombinant human erythropoietin). It was not possible to give all the information collected from the recent literature: since mild renal failure has little effect on the fate of a drug, pharmacokinetic data obtained in patients with a creatinine clearance (CLCR) of more than 50 ml/min has been omitted. Both the text and tables give recommendations for treating patients with moderate renal insufficiency (CLCR of about 50 ml/min), more severe renal impairment (CLCR between 10 and 50 ml/min) and end-stage renal failure with a very low creatinine clearance (below 10 ml/min). It was not possible to give uniform recommendations (i.e. reducing the dose while maintaining the same interval, or giving the same dose and prolonging the interval). This article follows the recommendations of the authors, which may vary for drugs in similar classes.

Incorporating Breastfeeding-Related Variability with Physiologically Based Pharmacokinetic Modeling to Predict Infant Exposure to Maternal Medication Through Breast Milk: a Workflow Applied to Lamotrigine

“…Two main lamotrigine metabolizing enzymes, UGT1A4 and UGT1A3, were incorporated and their relative contributions to clearance were allocated accordingly. Following optimization of the IV model, a PBPK model using 15 studies with lamotrigine single-dose oral administration ranging from 25-300 mg in adults (15,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) was built. Optimization of absorption-specific parameters (specific intestinal permeability, dissolution half-time) provided a final model.…”

Continuous Renal Replacement Therapy (CRRT) for Lithium Toxicity: An Alternative Treatment to Avoid Intradialytic Hypotension

“…However, any medication that is renally cleared has also been reported to contribute. Of the medications our patient was on chronically as well as ingested on admission, acyclovir levels are renally excreted and others such as risperidone are increased in impaired renal function (8)(9)(10)(11)(12)(13). It is possible that excess acyclovir causes renal impairment that compounded the serum levels of lithium in our patient's serum.…”

Continuous renal replacement therapy for lithium toxicity: A worthy treatment to avoid intradialytic hypotension and vasopressors

“…Of the medications our patient was on chronically as well as ingested on admission, acyclovir levels are renally excreted and others such as risperidone are increased in impaired renal function. [9][10][11][12][13][14] It is possible that excess acyclovir caused some renal impairment which in turn compounded the serum levels of lithium in our patient's serum.…”