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

Minocycline a
95-100 11 ± 2 76 1.0 ± 0.3 1.3 ± 0.2 b 16 ± 2 IV: 3.5 μg/mL c
a
Cleared primarily by oxidative metabolism in the liver. b V area
reported. c Following a single
200-mg IV infusion (1 hour) or range of values following a 100-mg oral dose given twice a
day to steady state.
Mirtazapine a
b HL b HL i HL
PO: 2-4 c
PO: 2.3-3.5 μg/mL c
50 ± 10 — 85 9.12 ± 1.14 b 4.5 ± 1.7 16.3 ± 4.6 b,e 1.5 ± 0.7 f 41.8 ± 7.7 ng/mL f
b LD, c RD d
b LD, c RD d
a
Data from healthy adult subjects. Metabolized by CYP2D6 and CYP1A2 (8-hydroxy) and
CYP3A (N-desmethyl, N-oxide). b Women of all ages exhibit a lower CL/F and longer t 1/2
than
men. c CL/F reduced, hepatic impairment. d CL/F reduced, moderate to severe renal impairment.
e The t 1/2
of the (−)-enantiomer is approximately twice as long as the (+)-antipode;
approximately 3-fold higher blood concentrations (+ versus −) are achieved. f Following a
15-mg oral dose given once daily to steady state.
Mitoxantrone a
— b ~2 97 13 ± 8 90 ± 42 c β-phase: 1.1 ± — 308 ± 133 ng/mL e
b LD
a
Data reported for patients treated for cancer. Information from older literature confounded by
nonspecific assays. b For parenteral administration only; usually given as a rapid IV infusion
every 3 months. c Reflects distribution into a “deep” tissue compartment. V c
is 0.3 ± 0.2 L/kg.
d
t 1/2
for the β-phase predicts time to steady state for short-term IV infusions. t 1/2
for the γ-
phase predicts long-term persistence in the body. e Following a single 30-minute IV infusion of
12-14 mg/m 2 .
Reference: Saivin S, et al. Clinical pharmacokinetics of doxycycline and minocycline. Clin
Pharmacokinet, 1988, 15:355–366.
References: Fawcett J, et al. Review of the results from clinical studies on the efficacy, safety
and tolerability of mirtazapine for the treatment of patients with major depression. J Affect
Disord, 1998, 51:267–285. PDR54, 2000, p. 2109.
1.1 d
γ-phase: 72 ± 40 d
a LD
References: Ehninger G, et al. Pharmacokinetics and metabolism of mitoxantrone. A review.
Clin Pharmacokinet, 1990, 18:365–380. Hu OY, et al. Pharmacokinetic and pharmacodynamic
studies with mitoxantrone in the treatment of patients with nasopharyngeal carcinoma.
Cancer, 1992, 69:847–853.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
1955