Table 4.
Main PK characteristics and suggestions for appropriate prescription in CKD patients for most used beta-blockers and antiarrhythmic drugs (modified from ref.78)
| Drug | PK and elimination | Indications for CKD |
|---|---|---|
| Atenolol | About 5% bound to plasma protein; T1/2 ∼6 h but action duration is 24 h; excreted unchanged in urine | Dose may need to be reduced |
| Bisoprolol | Approximately 30% bound to protein; peak plasma concentration in 2–4 h; metabolized by the liver but ∼50% excreted unchanged in urine | Monitoring; dose may need to be reduced in advanced CKD |
| Carvedilol | 99% protein bound; T1/2 ∼6–10 h; elimination mainly biliary and 16% urinary | Dosage adjustment usually not required excepting advanced renal failure and elderly |
| Labetalol | 90% protein bound; T1/2 ∼6–8 h metabolized by liver with inactive metabolites excreted in urine and bile; <5% excreted unchanged in urine | Dose reduction recommended in the elderly |
| Metoprolol | Approximately 12% protein bound; T1/2 ∼3–5 h but the effect persists for 12 h; <5% excreted unchanged in urine | No dosage reduction needed |
| Sotalol | Not protein bound; T1/2 ∼7–18 h; not metabolized; excreted unchanged in urine (∼70%) | Dose to be reduced to one half in CKD and one quarter in severe renal failure where there is relative contraindication in view of the risk of pro-arrhythmic effects |
| Procainamide | 15% protein bound; bounds to different tissues; active hepatic metabolite; variable hepatic and renal elimination (60% unchanged); longer elimination in renal failure | Reduction of dose recommended |
| Quinidine | 85% protein bound; 50–90% metabolized by the liver to active metabolites; T1/2 ∼6 h; 20% excreted in urine | Pro-arrhythmia; could interfere with renal clearance of other drugs |
| Lidocaine | 65% protein bound; 80% rapidly metabolized by the liver to active metabolites; T1/2 <2 h; <10% excreted unchanged in urine | No special requirements |
| Mexiletine | 50–70% protein bound; T1/2 ∼5–17 h; ∼15% excreted unchanged in urine | No special requirements |
| Flecainide | T 1/2 ∼20 h; metabolized by the liver and excreted unchanged in urine (35%) | Dose reduction if GFR <35 mL/min/1.73 m2 |
| Propafenone | 95% protein bound; metabolized by the liver to active metabolites, excreted in urine (38%); two genetically determined pathways of metabolism (>90% people are rapid metabolizers with T1/2 ∼2–10 h); <1% excreted unchanged in urine | Careful monitoring recommended (in hospital initiation if advanced CKD) |
| Vernakalant | 25–50% protein bound, extensively and rapidly distributed in the body after intravenous administration, not extensively bound to plasma proteins. Mainly eliminated by the liver with T1/2 ∼3–5.5 h | Available for intravenous administration at the dose of 3.0 mg/kg followed by 2.0 mg/kg if required |
| Amiodarone | 99% protein bound; widely distributed to different tissues; metabolized by the liver to two active metabolites; no renal elimination | No dosage requirements; not dialyzable; many drug-to-drug interactions |
| Dronedarone | ∼98% protein bound; metabolized by the liver to active and inactive metabolites; T1/2 ∼13–19 h; 6% excreted in urine | No dosage adaptation required in mild and severe renal failure |
| Dofetilide | High (>90%) bioavailability; protein binding of 60–70%; 80% excreted by the kidney, as unchanged dofetilide (80%) or as inactive or minimally active metabolites (20%); T1/2 ∼10 h | Dose individualized on the basis of GFR; contraindicated if GFR <20 mL/min |
| Diltiazem | 70–80% protein bound; extensive first-pass effect, metabolization in the liver to active metabolites; bioavailability of ∼40%; T1/2 ∼3.5–9 h; only 2–4% unchanged drug excreted in the urine | Use with caution |
| Verapamil | About 90% protein bound. High first-pass metabolism, Metabolized in the liver to at least 12 inactive metabolites. Bioavailability 10–35%. 70% is excreted in the urine and 16% in faeces. T1/2 ∼5–12 h | Dose reduction by 25–50% if CrCl <10 mL/min. Not cleared by haemodialysis |
| Adenosine | Rapid cell uptake and clearance; PK difficult to be studied; not dependent on renal function | No dosage adaptation required |
| Digoxin | 20–30% protein bound; T1/2 ∼26–45 h; main route of elimination is renal (closely correlated with the GFR) with 25–28% of elimination by non-renal routes | Dosage adaptation is required, with monitoring of serum digoxin levels |
CKD, chronic kidney disease; CrCl, creatinine clearance; GFR, glomerular filtration rate; PK, pharmacokinetics.