DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 29–5
Pharmacokinetic Characteristics and Doses of Anti-Arrhythmic Drugs (continued)
BIOAVAILABILITY ELIMINATION USUAL DOSES c
Reduced PROTEIN THERAPEUTIC b
First-Pass BINDING ELIMINATION ACTIVE PLASMA Maintenance
DRUG Metabolism >80% Renal Hepatic Other t 1/2
METABOLITE(S) CONCENTRATION Loading Doses Doses
Mexiletine >80% ✓ 9-15 h 0.5-2 g/mL 400 mg 200 mg/8 h
Procainamide >80% ✓ ✓ 3-4 h ✓ 4-8 g/mL 500-600 mg (IV), 2-6 mg/min (IV);
given at 20 250 mg q3h;
mg/min
500-1000 mg q6h
(N-Acetyl (>80%) (✓) (6-10 h) (10-20 g/mL)
procainamide)
Propafenone ✓ ✓ 2-32 h ✓ <1 g/mL 150 mg/8h
(immediate
release);
225 mg/12h
(extended release)
Propranolol ✓ ✓ ✓ 4 h 1-3 mg admin- 10-30 mg q6-8h
istered no faster (immediate
than 1 mg/min, release)
may repeat e after
2 min (IV)
Quinidine >80% −80% (x) ✓ 4-10 h ✓ 2-5 g/mL 648 mg (gluconate)
every 8h
Sotalol >80% ✓ 8 h <5 g/mL (?) 80-160 mg/12h
Verapamil ✓ ✓ ✓ 3-7 h ✓ 5-10 mg given 40-120 mg/6-8h
over 2 min or (immediate
more (IV)
release)
✓ Indicates an effect that affects the clinical action of the drug. (x): metabolite or route of elimination probably of minor clinical importance. *The elimination t 1/2
is one, but not the only, determinant
of how frequently a drug must be administered to maintain a therapeutic effect and avoid toxicity (Chapter 2). For some drugs with short elimination half-lives, infrequent dosing is nevertheless
possible, e.g., verapamil. Formulations that allow slow release into the GI tract of a rapidly eliminated compound (available for many drugs, including procainamide, disopyramide,
verapamil, diltiazem, and propranolol) also allow infrequent dosing. b The therapeutic range is bounded by a plasma concentration below which no therapeutic effect is likely, and an upper concentration
above which the risk of adverse effects increases. Many serious adverse reactions to anti-arrhythmic drugs can occur at “therapeutic” concentrations in susceptible individuals. When
only an upper limit is cited, a lower limit has not been well defined. Variable generation of active metabolites may further complicate the interpretation of plasma concentration data (Chapter 2).
c
Oral doses are presented unless otherwise indicated. Doses are presented as suggested ranges in adults of average build; lower doses are less likely to produce toxicity. Lower maintenance
dosages may be required in patients with renal or hepatic disease. Loading doses are only indicated when a therapeutic effect is desired before maintenance therapy would bring drug concentrations
into a therapeutic range—that is, for acute therapy (e.g., lidocaine, verapamil, adenosine) or when the elimination t 1/2
is extremely long (amiodarone). d Bioavailability reduced by incomplete
absorption. e Indicates suggested dosage using slow-release formulation. f This drug is available only in a restricted distribution system (see text). IV, intravenous.