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

Glipizide
95 <5 98.4 0.52 ± 0.18 a 0.17 ± 0.02 a 3.4 ± 0.7 2.1 ± 0.9 b 465 ± 139 ng/mL b
i RD, Aged i Aged i RD, Aged
a
CL/F and V ss
/F reported. b Following a single 5-mg oral dose (immediate-release tablet) given to
healthy young adults. An extended-release formulation exhibits a delayed T max
of 6-12 hours.
Glyburide
G: 90-100 a Negligible 99.8 1.3 ± 0.5 0.20 ± 0.11 4 ± 1 b G: ~1.5 c G: 106 ng/mL c
M: 64-90 a b Aged b LD a LD, NIDDM M: 2-4 c M: 104 ng/mL c
a
Data for GLYNASE PRESTAB micronized tablet (G) and MICRONASE tablet (M). b t 1/2
for G reported.
t 1/2
for M formulation is 6-10 hours, reflecting absorption rate limitation. A long terminal t 1/2
(15 hours), reflecting redistribution from tissues, has been reported. c Following a
3-mg oral GLYNASE tablet taken with breakfast or a 5-mg oral MICRONASE tablet given to
healthy adult subjects.
Haloperidol a
60 ± 18 1 92 ± 2 11.8 ± 2.9 b 18 ± 7 18 ± 5 b IM: 0.6 ± 0.1 c IM: 22 ± 18 ng/mL c
a LD a Child, Smk b Child PO: 1.7 ± 3.2 c PO: 9.2 ± 4.4 ng/mL c
i Aged, Child b Aged
a
Undergoes reversible metabolism to a less active reduced haloperidol. b Represents net CL of
parent drug; reduced haloperidol CL = 10 ± 5 mL · min –1 ·kg –1 and t 1/2
= 67 ± 51 hours. Slow
conversion from reduced haloperidol to parent compound probably responsible for prolonged
Heparin
Reference: Kobayashi KA, et al. Glipizide pharmacokinetics in young and elderly volunteers.
Clin Pharm, 1988, 7:224–228.
References: Jonsson A, et al. Slow elimination of glyburide in NIDDM subjects. Diabetes
Care, 1994, 17:142–145. Drugs@FDA.GLYNASE PRETAB label; http://www.accessdata.
fda.gov/drugsatfda_docs/label/2009/020051s0161bl.pdf. Accessed July 10, 2010.
terminal t 1/2
(70 hours) for haloperidol observed with 7-day sampling. c Following a single
20-mg oral or 10-mg IM dose. Effective concentrations are 4-20 ng/mL.
Reference: Froemming JS, et al. Pharmacokinetics of haloperidol. Clin Pharmacokinet, 1989,
17:396–423.
— Negligible Extensive 1/(0.65 + 0.008D) 0.058 ± 0.11 b (26 + 0.323D) ± 3 c 70 ± 39 ng/mL c
± 0.1 a 12 min a
b Fem
b Smk
a
Dose (D) is in IU/kg. CL and t 1/2
are dose dependent, perhaps due to saturable metabolism
with end-product inhibition. b V area
reported. c Mean of above critical length molecules following
a single 5000 IU dose (unfractionated) given by SC injection.
References: Bendetowicz AV, et al. Pharmacokinetics and pharmacodynamics of a low molecular
weight heparin (enoxaparin) after subcutaneous injection, comparison with unfractionated
heparin—A three way cross over study in human volunteers. Thromb Haemost, 1994,
71:305–313. Estes JW. Clinical pharmacokinetics of heparin. Clin Pharmacokinet, 1980,
5:204–220.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
1937