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

1982
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
Tenofovir a
25 b 82 ± 13 <1 2.6 ± 0.9 c 0.6 ± 0.1 c 8.1 ± 1.8 c,d 2.3 e 326 ng/mL e
a Food b RD a RD
a
Tenofovir is formulated as an ester prodrug, VIREAD (tenofovir disoproxil fumarate), for oral
administration. b Bioavailability under fasted state reported; increased to 39% with high-fat
meal. c Data reported for steady-state 3-mg/kg IV dose given once a day for 2 weeks to HIV-1-
infected male and female adults. Slightly higher CL with single IV dose. d Longer apparent
plasma t 1/2
(17 hours) reported for steady-state oral dosing; this may reflect a longer duration
of blood sampling; also, phosphorylated “active” metabolite exhibits a longer intracellular
t 1/2
(60 hours). e Following a 300-mg oral dose given once a day with a meal to steady state.
References: Barditch-Crovo P, et al. Phase i/ii trial of the pharmacokinetics, safety, and
Terazosin
82 11-14 90-94 1.1-1.2 a 1.1 9-12 1.7 b 16 ng/mL b
a
Plasma CL reportedly reduced in patients with hypertension. b Following a 1-mg oral dose
(tablet) given to healthy volunteers.
Thalidomide a
— b <1 — 2.2 ± 0.4 c 1.1 ± 0.3 c 6.2 ± 2.6 c 3.2 ± 1.4 d 2.0 ± 0.6 μg/mL d
a HD, Food a HD
a
Data from healthy male subjects. Similar data reported for asymptomatic patients with HIV. References: Noormohamed FH, et al. Pharmacokinetics and hemodynamic effects of single
No age or gender differences. Thalidomide undergoes spontaneous hydrolysis in blood to oral doses of thalidomide in asymptomatic human immunodeficiency virus-infected subjects.
multiple metabolites. b Absolute bioavailability is not known. Altered absorption rate and AIDS Res Hum Retrovir, 1999, 15:1047–1052. PDR54, 2000, p. 912. Teo SK, et al. Singledose
extent, Hansen’s disease (HD). c CL/F, V area
/F, and t 1/2
reported for oral dose. d Following a
oral pharmacokinetics of three formulations of thalidomide in healthy male volunteers.
single 200-mg oral dose.
J Clin Pharmacol, 1999, 39:1162–1168.
Tigecycline a
antiretroviral activity of tenofovir disoproxil fumarate in human immunodeficiency virusinfected
adults. Antimicrob Agents Chemother, 2001, 45:2733–2739. Deeks SG, et al. Safety,
pharmacokinetics, and antiretroviral activity of intravenous 9-[2-(R)-(Phosphonomethoxy)
propyl]adenine, a novel anti-human immunodeficiency virus (HIV) therapy, in HIV-infected
adults. Antimicrob Agents Chemother, 1998, 42:2380–2384. Kearney BP, et al. Tenofovir
disoproxil fumarate: Clinical pharmacology and pharmacokinetics. Clin Pharmacokinet,
2004, 43:595–612.
References: Senders RC. Pharmacokinetics of terazosin. Am J Med, 1986, 80:20–24. Sennello
LT, et al. Effect of age on the pharmacokinetics of orally and intravenously administered terazosin.
Clin Ther, 1988, 10:600–607.
— 22 b 71-89 3.3 ± 0.3 c 7.2 ± 0.5 c 36.9 ± 11.8 c — 621 ± 93 ng/mL c
a
Tigecycline is a glycylcycline, a new tetracycline class of antibiotic. Tigecycline undergoes
minimal metabolism; major routes of elimination are via biliary and urinary excretion.
b
Percent of dose excreted as unchanged drug in urine. c At steady state during repetitive 50-mg
IV doses of tigecycline infused over a 1-hour period given every 12 hours.
References: Drugs@FDA. Tygacil label approved on 3/20/09. Available at:
http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed on December 31,
2009. Muralidharan G, et al. Pharmacokinetics of tigecycline after single and multiple doses
in healthy subjects. Antimicrob Agents Chemother, 2005, 49:220–229.