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
Foscarnet
9 ± 2 95 ± 5 14-17 1.6 ± 0.2 0.35 5.7 ± 0.2 1.4 ± 0.6 b 86 ± 36 μM b
b RD a
a RD a
a
In patients with moderate to severe renal impairment. b Following an 8-mg/kg oral dose given
once daily for 8 days to HIV-seropositive patients.
References: Aweeka FT, et al. Effect of renal disease and hemodialysis on foscarnet pharmacokinetics
and dosing recommendations. J Acquir Immune Defic Syndr Hum Retrovirol, 1999,
Fosfomycin a
28 ± 8 82 ± 13 Negligible 2.31 ± 0.22 0.36 ± 0.06 2.2 ± 0.5 2.0 ± 0.6 d 21.8 ± 4.8 μg/mL d
(28-41)
b Food b b RD c a RD c a Food b b Food b
a
Fosfomycin is cleared predominantly by renal elimination. Data from adult male subjects. No
significant gender differences. Range of mean values from multiple studies shown in parentheses.
b High-fat meal. c CL/F reduced in patients with mild to severe renal impairment.
d
Following a single 3-g oral dose of fosfomycin trometamol in healthy adults.
Fulvestrant a
20:350–357. Noormohamed FH, et al. Pharmacokinetics and absolute bioavailability of oral
foscarnet in human immunodeficiency virus-seropositive patients. Antimicrob Agents
Chemother, 1998, 42:293–297.
References: Bergan T, et al. Pharmacokinetic profile of fosfomycin trometamol. Chemotherapy,
1993, 39:297–301. Cadorniga R, et al. Pharmacokinetic study of fosfomycin and its bioavailability.
Chemotherapy, 1977, 23:159–174. Goto M, et al. Fosfomycin kinetics after intravenous
and oral administration to human volunteers. Antimicrob Agents Chemother, 1981, 20:393–397.
PDR54, 2000, p. 1083.
— b <1 99 9.3-14.3 3.0-5.3 14-19 c 167 d 8.2 ± 5.2 ng/mL d
a
Eliminated by conjugation (sulfate and glucuronide) and CYP3A4-mediated oxidation. Data
reported for men and women; no significant gender differences. b For parenteral administration
only. Bioavailability following IM injection has not been reported. c Elimination t 1/2
following IV
administration. The apparent t 1/2
following IM dosing is ~40 days due to very prolonged absorption.
d Following a single 250-mg IM dose given to postmenopausal women with breast cancer.
References: PDR58, 2004, pp. 669–670. Robertson JF, et al. Fulvestrant: Pharmacokinetics
and pharmacology. Br J Cancer, 2004, 90(suppl):S7–S10. Robertson JF, et al.
Pharmacokinetic profile of intramuscular fulvestrant in advanced breast cancer. Clin
Pharmacokinet, 2004, 43:529–538.