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

1924
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
Doxorubicin a
5 <7 76 666 ± 339 mL/ 682 ± 433 26 ± 17 b — High c
min/m 2 L/m 2 D: ~950 ng/mL
i LD i RD DL: 30-1008 ng/mL
Doxycycline
a Child
b LD, Obes
a
Active metabolites; t 1/2
for doxorubicinol is 29 ± 16 hours. b Prolonged when plasma bilirubin
concentration is elevated; undergoes biliary excretion. c Mean data for doxorubicin (D) and
range of data for doxorubicinol (DL). High: a single 45- to 72-mg/m 2 high-dose 1-hour IV
infusion given to patients with small cell lung cancer. Low: continuous IV infusion at a rate
of 3.9 ± 0.65 mg/m 2 /day for 12.4 (2-50) weeks to patients with advanced cancer.
a LD
Low c
D: 6.0 ± 3.2 ng/mL
DL: 5.0 ± 3.5 ng/mL
93 41 ± 19 88 ± 5 0.53 ± 0.18 0.75 ± 0.32 16 ± 6 Oral: 1-2 b IV: 2.8 μg/mL b
b RD a b HL, Aged b HL, Aged i RD, HL, Aged PO: 1.7-2 μg/mL b
i RD
a
Decreases in plasma protein binding to 71 ± 3% in patients with uremia. b Mean data following
a single 100-mg IV dose (1-hour infusion) or range of mean data following a 100-mg oral
dose given to adults.
Dronabinol a
References: Ackland SP, et al. Pharmacokinetics and pharmacodynamics of long-term
continuous-infusion doxorubicin. Clin Pharmacol Ther, 1989, 45:340–347. Piscitelli SC, et al.
Pharmacokinetics and pharmacodynamics of doxorubicin in patients with small cell lung cancer.
Clin Pharmacol Ther, 1993, 53:555–561.
Reference: Saivin S, et al. Clinical pharmacokinetics of doxycycline and minocycline. Clin
Pharmacokinet, 1988, 15:355–366.
10-20 Trace ~97 7.8 ± 1.9 b 8.9 ± 4.2 α: 2.8 ± 1.8 2.5 (0.5-4.0) f 3.0 ± 1.8 ng/mL f
β: 20 ± 4 d
a Chronic c
i Chronic e
a
Cleared primarily by cytochrome P450-dependent metabolism; evidence suggests polymorphic
70:1096–1103. Drugs@FDA. Marinol label approved on 6/21/06.
CYP2C9 is a major contributor. b Somewhat lower values (2.8-3.5 mL/min/kg) also were http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/018651s025s026lbl.pdf. Accessed
reported, but a higher systemic clearance is most consistent with the low oral bioavailability. May 17, 2010. Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids.
c
Study in long-term users of THC. d Exhibits biphasic kinetics; the longer terminal elimination Clin Pharmacokinet, 2003, 42:327–360. Hunt CA, et al. Tolerance and disposition of tetrahydrocannabinol
phase most likely represents redistribution from fatty tissue. e No change in terminal (redistribution)
in man. J Pharmacol Exp Ther, 1980, 215:35–44. Wall ME, et al. Metabolism,
t 1/2
. f Following a 5-mg dose given twice daily to steady state.
disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women. Clin Pharmacol
References: Bland TM, et al. CYP2C-catalyzed delta9-tetrahydrocannabinol metabolism:
Ther, 1983, 34:352–363.
Kinetics, pharmacogenetics and interaction with phenytoin. Biochem Pharmacol, 2005,