Renal insufficiency drug distribution

Drug therapy individualization for patients with renal insufficiency sometimes requires only a simple proportional dose adjustment based on creatinine clearance (CLcr). Alternatively, complex adjustments are required for drugs that are extensively metabolized or undergo dramatic changes in protein binding and distribution volume. 

Methods for calculating volume of distribution (VD) can be influenced by renal disease. Of the commonly used terms (i.e., volumes of central compartment, terminal phase, and distribution at steady state [ Vss]), Vss is the most appropriate for comparing patients with renal insufficiency versus those with normal renal function because Vss is independent of drug elimination. 

Vancomycin is poorly absorbed from the intestinal tract and is administered orally only for the treatment of antibiotic-associated enterocolitis caused by Clostridium difficile. Parenteral doses must be administered intravenously. A 1 hour intravenous infusion of 1 g produces blood levels of 15-30 jig/mL for 1-2 hours. The drug is widely distributed in the body. Cerebrospinal fluid levels 7-30% of simultaneous serum concentrations are achieved if there is meningeal inflammation. Ninety percent of the drug is excreted by glomerular filtration. In the presence of renal insufficiency, striking accumulation may occur (Table 43-2). In functionally anephric patients, the... 

In Belgium, the distribution of analgesic nephropathy in patients with terminal renal insufficiency was well correlated with the sale of drugs containing either aspirin -I- phenacetin or paracetamol + caffeine (SEDA-7,75), and it is estimated that Belgium, after Australia, had the second highest incidence of analgesic nephropathy in the world. 

The volume of distribution of many drugs may be significantly increased or decreased in patients with renal insufficiency (Table 48-1) 8,12,13. Iterations in distribution volume may result from increased or decreased protein binding altered tissue binding or pathophysio-... 

Finally, the method used to calculate the volume of distribution may be influenced by renal insufficiency. The three most commonly used volume of distribution terms are volume of the central compartment (Ec), volume of the terminal phase (E, E jea). and volume of distribution at steady state (Eis). The central compartment volume is calculated as the intravenous bolus dose divided by the initial plasma concentration. E for many drugs approximates extracellular fluid volume and thus may be increased or decreased by shifts in this physiologic volume. Renal insufficiency, especially oliguric acute renal failure, is often accompanied by fluid overload and a resultant increased Ec due to reduced renal elimination of water and sodium. Uaiea Or E is Calculated as the total body clearance divided by the terminal elimination rate constant (k or /3). This volume term represents the proportionality constant between plasma concentrations in the terminal elimination phase and the amount of drug remaining in the body. E is affected by both distribution characteristics, as well as by the elimination rate constant. The third volume term, the steady-state volume of distribution (Ess), is calculated as (AUMC x dose)/AUC , where AUMC is the area under the first moment of the concentrationtime curve and AUC is the area under the concentration-time curve... 

If the volume of distribution (Vu) of a drug is significantly altered in patients with renal insufficiency or in whom one desires to attain a specific maximum or minimum concentration, the estimation of a dosage regimen becomes more complex. If the relationship between... 

When given orally, 70—90% of cycloserine is rapidly absorbed. Cycloserine is distributed throughout body fluids and tissues. CSF concentrations are comparable to those in plasma. About 50% of a parenteral dose of cycloserine is excreted unchanged in the urine in the first 12 hours a total of 65% is recoverable in the active form over a period of 72 hours. Very little of the antibiotic is metabolized. The drug may reach toxic concentrations in patients with renal insufficiency it is removed from the circulation by hemodialysis. 

In Fig. 4.7, please note the differences in the slope of the concentration versus time data, which will be reflected in the elimination rate constant and the elimination half life of the drug. Questions for reflection Is the initial plasma concentration of the drug also affected by the renal insufficiency Will the apparent volume of drug distribution be different in three subjects Will the systemic clearance of this drug be different in each subject Will the area under the plasma concentration (AUC)o be different in each subject ... 

The Pharmacokinetics section of each chapter covers absorption, tissue distribution, elimination, and body fluid concentrations. Such pharmacokinetic information is usually not included in other sources and may be useful in forensic investigations or in the clinical setting regarding use of the product in patients with renal or hepatic insufficiency. A section on Adverse Effects and Toxicity follows and includes detailed information on case reports of adverse reactions to the herb. The Interactions section includes discussions of interactions between the supplement and drugs or foods. The Reproduction section follows and is generally limited because of lack of information. Each chapter ends with a discussion of Regulatory Status of the product. The amount of information included in each of these sections varies according to availability. 

---