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

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APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
Table AII–1
Pharmacokinetic Data (Continued)
BIOAVAILABILITY URINARY BOUND IN CLEARANCE VOL. DIST. HALF-LIFE PEAK TIME PEAK
(ORAL) (%) EXCRETION (%) PLASMA (%) (mL/min/kg) (L/kg) (hours) (hours) CONCENTRATION
Interferon Beta
SC: 51 ± 17 — a — 13 ± 5 a 2.9 ± 1.8 4.3 ± 2.3 SC: 1-8 b IV: 1491 ± 659
IU/mL b
a
Undergoes renal filtration, tubular reabsorption, and renal catabolism, but hepatic uptake and
catabolism are thought to dominate systemic CL. b Concentration at 5 minutes following a single
90 × 10 6 IU IV dose or following a single 90 × 10 6 IU SC dose of recombinant interferon
beta-1b.
Irbesartan a
SC: 40 ± 20 IU/mL b
60-80 2.2 ± 0.9 90 2.12 ± 0.54 0.72 ± 0.20 13 ± 6.2 1.2 (0.7-2) c 1.3 ± 0.4 μg/mL c
b Aged b
i RD, LD
a
Data from healthy male subjects. No significant gender differences. Metabolized by UGT
and CYP2C9. b CL/F reduced; no dose adjustment required. c Following a single 50-mg oral
dose (capsule).
References: Gillis JC, et al. Irbesartan. A review of its pharmacodynamic and pharmacokinetic
properties and therapeutic use in the management of hypertension. Drugs, 1997, 54:885–902.
Irinotecan a
Reference: Chiang J, et al. Pharmacokinetics of recombinant human interferon-β ser
in healthy
volunteers and its effect on serum neopterin. Pharm Res, 1993, 10:567–572.
PDR54, 2000, p. 818. Vachharajani NN, et al. Oral bioavailability and disposition characteristics
of irbesartan, an angiotensin antagonist, in healthy volunteers. J Clin Pharmacol, 1998,
38:702–707.
— I: 16.7 ± 1.0 I: 30-68 I: 14.8 ± 4 L/hr/m 2 I: 150 ± 49 L/m 2 I: 10.8 ± 0.5 I: 0.5 b I: 1.7 ± 0.8 μg/mL b
SN-38: 95 SN-38: 10.4 ± 3.1 SN-38: ≤1 b SN-38: 26 ±
12 ng/mL b
a
Data from male and female patients with malignant solid tumors. No significant gender differences.
Irinotecan (I) is metabolized to an active metabolite, SN-38 (100-fold more potent
but with lower blood levels). b Following a 125-mg/m 2 IV infusion over 30 minutes.
References: Chabot GG, et al. Population pharmacokinetics and pharmacodynamics of irinotecan
(CPT-11) and active metabolite SN-38 during phase I trials. Ann Oncol, 1995, 6:141–151.
PDR54, 2000, pp. 2412–2413.