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

Table 56–2
Population Pharmacokinetic Parameter Estimates for Antimycobacterial Drugs in Adult Patients
PARAMETER ESTIMATE
k a
(h −1 ) SCL (L/h) V d
(L)
First-line Drugs
Rifampin 1.15 19 53
Rifapentine 0.6 2.03 37.8
Rifabutin 0.2 61 231/1,050 a
Pyrazinamide 3.56 3.4 29.2
Isoniazid 2.3 22.1 35.2
Ethambutol 0.7 1.3 b 6.0 b
Clofazimine 0.7 0.6/76.7 1470
Dapsone 1.04 1.83 69.6
Second-line Agents
Ethionamide 0.25 1.9 b 3.2 b
Para-aminosalicylic acid 0.4 0.3 b 0.9 b
Cycloserine 1.9 0.04 b 0.5 b
ªVolume of central compartment/volume of peripheral compartment. b Expressed per kilogram of body weight. k a
, absorption constant (see Chapter 48);
SCL, systemic clearance; V d
, volume of distribution.
1553
Table 56–3
Pharmacokinetic Parameters of Rifampin, Rifabutin, and Rifapentine
RIFABUTIN RIFAMPIN RIFAPENTINE
Protein binding (%) 71 85 97
Oral bioavailability (%) 20 68 —
t max
(hours) 2.5-4.0 1.5-2.0 5.0-6.0
C max
total (μg/mL) 0.2-0.6 8-20 8-30
C max
free drug (μg/mL) 0.1 1.5 0.5
Half-life (hours) 32-67 2-5 14-18
Intracellular/extracellular penetration 9 5 24-60
Autoinduction (AUC decrease) 40% 38% 20%
CYP3A induction Weak Pronounced Moderate
CYP3A substrate Yes No No
AUC, area under the curve.
25% of patients with severe HIV infection who received rifabutin.
Uveitis and arthralgias have occurred in patients receiving rifabutin
doses >450 mg daily in combination with clarithromycin or fluconazole.
Patients should be cautioned to discontinue the drug if visual
symptoms (pain or blurred vision) occur. Rifabutin causes an
orange-tan discoloration of skin, urine, feces, saliva, tears, and contact
lenses, like rifampin. Rarely, thrombocytopenia, a flu-like syndrome,
hemolysis, myositis, chest pain, and hepatitis develop in
patients treated with rifabutin. Unique side effects include polymyalgia,
pseudojaundice, and anterior uveitis.