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

Vancomycin
— a 79 ± 11 30 ± 11 CL = 0.79CL cr
+ 0.39 ± 0.06 5.6 ± 1.8 — 18.5 (15-25) μg/mL b
0.22
i RD b RD, Aged, Neo b Obes a RD, Aged
i Obes, CPBS i RD, CPBS b Obes
a Burn
a
Very poorly absorbed after oral administration, but used by this route to treat Clostridium difficile
and staphylococcal enterocolitis. b Following a dose of 1000-mg IV (1-hour infusion)
given twice daily or a 7.5-mg/kg IV (1-hour infusion) given four times daily to adult patients
with staphylococcal or streptococcal infections. Levels of 37-152 μg/mL have been associated
with ototoxicity.
Vardenafil a
15 (8-25) 2-6 93-95 (parent 56 3.0 b 4-5 (parent 0.7 (0.25-3) c 19.3 ± 1.7 ng/mL c
and M1) and M1)
a
Vardenafil is primarily metabolized by CYP3A with minor involvement of CYP2C9. The major
oxidative metabolite (M1), a product of N-desmethylation at the piperazine ring, is a less potent
PDE5 inhibitor and circulates at a level 28% that of the parent drug. It contributes only 7% of
the in vivo activity of vardenafil. b V ss
of 208 L, assuming 70-kg bodyweight. c Following a single
20-mg dose. There is no change in pharmacokinetics between single and multiple dosing.
Varenicline a
Reference: Leader WG, et al. Pharmacokinetic optimisation of vancomycin therapy. Clin
Pharmacokinet, 1995, 28:327–342.
≥87% b 86.2 ± 6.2 ≤20 2.27 ± 0.34 c 6.2 c 31.5 ± 7.7 c 2.0 (1.0-4.0) d 10.2 ± 1.0 ng/mL d
a
Varenicline is eliminated mostly by renal excretion with minimal metabolism. Organic
Cation Transporter 2 (OCT2) is involved in renal tubular secretion, as evidenced by inhibition
of varenicline renal clearance by cimetidine, a known OCT2 inhibitor. b 87.1 ± 5.5% of
radioactivity is excreted in urine after an oral dose of [ 14 C]-varenicline. Minimal first-pass
metabolism is expected. c CL/F and V z
/F estimated from steady-state AUC and t 1/2
during 1-
mg twice-daily dosing of varenicline in healthy adult smokers and assuming an average body
weight of 70 kg. d After the first dose of a multiple-dosing regimen. An accumulation factor of
2.85 ± 0.73 was reported.
References: Drugs@FDA. Levitra label approved on 3/19/08. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm.
Accessed on December 31, 2009. Gupta M,
et al. The clinical pharmacokinetics of phosphodiesterase-5 inhibitors for erectile dysfunction.
J Clin Pharmacol, 2005, 45:987–1003.
References: Drugs@FDA. Chantix label approved on 7/1/09. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm.
Accessed on December 31, 2009. Faessel HM,
et al. Multiple-dose pharmacokinetics of the selective nicotinic receptor partial agonist,
varenicline, in healthy smokers. J Clin Pharmacol, 2006, 46:1439–1448. Obach RS, et al.
Metabolism and disposition of varenicline, a selective α4β2 acetylcholine receptor partial
agonist, in vivo and in vitro. Drug Metab Dispos, 2006, 34:121–130.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
1987