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

Lorazepam
93 ± 10 <1 91 ± 2 1.1 ± 0.4 a 1.3 ± 0.2 b 14 ± 5 IM: 1.2 c IV: ~75 ng/mL c
b LD, RD i Aged, Cirr, a LD, Burn, a LD, Neo, RD PO: 1.2-2.6 c IM: ~30 ng/mL c
AVH, Smk, RD CF, RD
i Aged, Burn i Aged, CPBS, PO: ~28 ng/mL c
AVH
a Burn, CF i Aged, AVH b Burn
a
Eliminated primarily by glucuronidation. b V area
reported. c Following a single 2-mg IV bolus
dose, IM dose, or oral dose given to healthy adults.
Losartan a
L: 35.8 ± 15.5 L: 12 ± 2.8 L: 98.7 L: 8.1 ± 1.8 L: 0.45 ± 0.24 L: 2.5 ± 1.0 L: 1.0 ± 0.5 d L: 296 ± 217 ng/mL d
LA: 99.8 b RD, b LD c LA: 5.4 ± 2.3 LA: 4.1 ± 1.6 d LA: 249 ± 74 ng/mL d
a
Data from healthy male subjects. Losartan (L) is metabolized primarily by CYP2C9 to an
active 5-carboxylic acid metabolite (LA). b CL/F for L but not LA decreased in severe renal
impairment (L/LA not removed by hemodialysis). No dose adjustment required. c CL/F for L
reduced in mild to moderate hepatic impairment. LA AUC also increased. d Following a single
Lovastatin a
≤5 10 >95 4.3-18.3 b — 1-4 AI: 2.0 ± 0.9 c AI: 41 ± 6 ng-Eq/mL c
a Food b RD TI: 3.1 ± 2.9 c TI: 50 ± 8 ng-Eq/mL c
a
Lovastatin is an inactive lactone that is metabolized to the corresponding active β-hydroxy
acid. Pharmacokinetic values are based on the sum of 3-hydroxy-3-methylglutaryl–coenzyme
A (HMG-CoA) reductase inhibition activity by the β-hydroxy acid and other less potent
metabolites. b The lactone (in equilibrium with β-hydroxy acid metabolite) is metabolized by
CYP3A. c Following an 80-mg oral dose given once daily for 17 days. Peak levels represent
total active inhibitors (AI) and total inhibitors (TI) of HMG-CoA reductase.
Maraviroc a
Reference: Greenblatt DJ. Clinical pharmacokinetics of oxazepam and lorazepam. Clin
Pharmacokinet, 1981, 6:89–105.
50-mg oral dose (tablet). Higher plasma levels of L (but not LA) in female subjects than in
male subjects.
References: Lo MW, et al. Pharmacokinetics of losartan, an angiotensin II receptor antagonist,
and its active metabolite EXP3174 in humans. Clin Pharmacol Ther, 1995, 58:641–649.
PDR54, 2000, pp. 1809–1812.
23-33 8.3 b 76 10.5 ± 1.3 2.8 ± 0.9 13.2 ± 2.8 3.1 (0.5-4.0) 1177 (895-
1459) ng/mL c
a
Cleared primarily by metabolism, with CYP3A4 being the major cytochrome P450 enzyme
mediating the N-dealkylation of maraviroc. b The fraction of dose excreted unchanged
increases from 1.5-12% with increasing doses (1- to 1200-mg single oral doses). c Following a
600-mg oral dose once daily for 7 days.
References: Corsini A, et al. New insights into the pharmacodynamic and pharmacokinetic
properties of statins. Pharmacol Ther, 1999, 84:413–428. Desager JP, et al. Clinical pharmacokinetics
of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. Clin
Pharmacokinet, 1996, 31:348–371. McKenney JM. Lovastatin: A new cholesterol-lowering
agent. Clin Pharm, 1988, 7:21–36.
References: Abel S, et al. Assessment of the absorption, metabolism and absolute bioavailability of
maraviroc in healthy male subjects. Br J Clin Pharmacol, 2008, 65(suppl 1):60–67. Abel S, et al.
Assessment of the pharmacokinetics, safety and tolerability of maraviroc, a novel CCR5 antagonist,
in healthy volunteers. Br J Clin Pharmacol, 2008, 65(suppl 1):5–18. Hyland R, et al. Maraviroc: In
vitro assessment of drug-drug interaction potential. Br J Clin Pharmacol, 2008, 66:498–507.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
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