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

Ivermectin a
— <1 93.1 ± 0.2 2.06 ± 0.81 b 9.91 ± 2.67 b 56.5 ± 7.5 b 4.7 ± 0.5 c 38.2 ± 5.8 ng/mL c
a
Data from male and female patients treated for onchocerciasis. Metabolized by hepatic
enzymes and excreted into bile. b CL/F, V area
/F, and t 1/2
reported for oral dose. Terminal
t 1/2
reported. c Following a single 150-μg/kg oral dose (tablet).
Ketorolac a
100 ± 20 5-10 99.2 ± 0.1 0.50 ± 0.15 0.21 ± 0.04 5.3 ± 1.2 IM: 0.7-0.8 c IM: 2.2-3.0 μg/mL c
b Aged, RD b a Aged, RD b PO: 0.3-0.9 c PO: 0.8-0.9 μg/mL c
i LD
i LD
a
Racemic mixture; S-(–)-enantiomer is much more active than the R-(+)-enantiomer.
Following IM injection, the mean AUC ratio for S/R-enantiomers was 0.44 ± 0.04, indicating
a higher CL and shorter t 1/2
for the S-(–)-enantiomer. Values reported are for the racemate.
b
Probably due to the accumulation of glucuronide metabolite, which is hydrolyzed back to
Lamotrigine a
97.6 ± 4.8 10 56 0.38-0.61 b,c 0.87-1.2 24-35 c 2.2 ± 1.2 f 2.5 ± 0.4 μg/mL f
b LD, d RD e
a LD, d RD e
a
Lamotrigine is eliminated primarily by glucuronidation. The parent-metabolite pair may
undergo enterohepatic recycling. Data from healthy adults and patients with epilepsy. Range
of mean values from multiple studies reported. b CL/F increases slightly with multiple-dose
therapy. c CL/F increased and t 1/2
decreased in patients receiving enzyme-inducing anticonvulsant
drugs. d CL/F reduced, moderate to severe hepatic impairment. e CL/F reduced, severe RD.
f
Following a single 200-mg oral dose to healthy adults.
Leflunomide a
References: Okonkwo PO, et al. Protein binding and ivermectin estimations in patients with
onchocerciasis. Clin Pharmacol Ther, 1993, 53:426–430. PDR54, 2000, p. 1886.
parent drug. c Range of mean C max
and T max
from different studies following a single 30-mg IM
or 10-mg oral dose in healthy adults. Reference: Brocks DR, et al. Clinical pharmacokinetics
of ketorolac tromethamine. Clin Pharmacokinet, 1992, 23:415–427.
References: Chen C, et al. Pharmacokinetics of lamotrigine in children in the absence of other
antiepileptic drugs. Pharmacotherapy, 1999, 19:437–441. Garnett WR. Lamotrigine:
Pharmacokinetics. J Child Neurol, 1997, 12(suppl 1):S10–S15. PDR54, 2000, p. 1209.
Wootton R, et al. Comparison of the pharmacokinetics of lamotrigine in patients with chronic
renal failure and healthy volunteers. Br J Clin Pharmacol, 1997, 43:23–27.
— b Negligible 99.4 0.012 c 0.18 (0.09-0.44) c 377 (336-432) d 6-12 e 35 μg/mL e
b RD a RD a RD i RD
a
Leflunomide is a prodrug that is converted almost completely (~95%) to an active metabolite
A77–1726 (2-cyano-3-hydroxy-N-(4-trifluoromethylphenyl)-crotonamide). All pharmacokinetic
data reported are for the active metabolite. b Absolute bioavailability is not known; parent
drug/metabolite are well absorbed. c Apparent CL/F and V/F in healthy volunteers reported.
Both parameters are a function of the bioavailability of leflunomide and the extent of its
conversion to A77–1726. d In patients with RA. e Following a 20-mg oral dose given once daily
to steady state in patients with RA.
Reference: Rozman B. Clinical pharmacokinetics of leflunomide. Clin Pharmacokinet, 2002,
41:421–430.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
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