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Source: Matzke
GR. Drug Therapy Individualization for Patients with Chronic Kidney
Disease. In: DiPiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG,
Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 8th edition. http://accesspharmacy.com/content.aspx?aid=7983360 and
Dager W, Halilovic J. Acute Kidney Injury. In: DiPiro, JT, Talbert
RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic
Approach. 8th edition. http://accesspharmacy.com/content.aspx?aid=7980960.
Accessed August 15, 2012.
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- Chronic kidney disease (CKD) causes changes in disposition
of some drugs as result of changes in bioavailability, distribution
volume, and metabolic activity.
- Drug therapy individualization (DTI) may involve:
- Simple proportional dose adjustment based on creatinine clearance
(CLcr) or glomerular filtration rate (GFR)
- Complex adjustments for drugs extensively metabolized or undergoing
dramatic changes in protein binding and distribution volume.
- Patient response to given drug may differ because of physiologic
and biochemical changes associated with CKD.
- Goals of DTI: design drug regimens to optimize therapeutic
outcomes and minimize adverse effects.
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- Drug absorption
- Little quantitative information
available
- Bioavailability theoretically affected by:
- Alterations
in gastrointestinal (GI) transit time
- Gastric pH
- Edema of GI tract
- Vomiting and diarrhea
- Concomitant drug therapy, especially antacid or H2-antagonist
administration
- Drug distribution
- CKD significantly increases
or decreases volume of distribution.
- Plasma protein binding of acidic drugs (e.g., warfarin,
phenytoin) is decreased in end-stage renal disease (ESRD).
- Monitor drug concentrations of free (unbound) drug.
- Binding of basic drugs (e.g., quinidine) is usually normal
or slightly increased or decreased.
- Method to calculate volume of distribution (VD) can
be influenced by renal disease.
- Use distribution
at steady state (VSS) to compare patients with renal insufficiency
to others with normal renal function.
- VSS is independent of drug elimination.
- Metabolism
- CKD may decrease nonrenal clearance
of drugs to greater degree than seen in AKI (Table 1).
- Severe renal insufficiency can cause accumulation of metabolites
that contributes to pharmacologic activity or toxicity.
- Excretion
- Renal clearance of drug is composite
of GFR, tubular secretion, and reabsorption.
- Importance of altered renal function on drug elimination depends
on fraction of drug normally eliminated unchanged by kidneys and
degree of renal insufficiency.
- Difficult to quantify contribution of tubular function to
renal drug clearance.
- Clinical measurement or estimation of CLcr or GFR
remains guiding factor for drug dosage regimen design.
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