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

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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
Mefloquine a
— b <1 98.2 0.43 ± 0.14 c 19 ± 6 c 20 ± 4 days SD: 7-19.6 d SD: 800-1020 ng/mL d
a Preg b Preg MD: 12 ± 8 d MD: 420 ±
i Child i Child 141 ng/mL d
a
Racemic mixture; no information on relative kinetics of the enantiomers. b Absolute bioavailability
is not known; reported values of >85% represent comparison of oral tablet to solution.
c
CL/F and V ss
/F reported. d Range of mean values from different studies following a single
Memantine a
~100 48 b 45 2.1 ± 0.4 c 10.9 e 64 ± 10 7.6 ± 3.7 22 ± 5 ng/mL g
b RD d
a RD f
a
Cleared primarily by the kidney and to a lesser extent by non-cytochrome P450-dependent
metabolism. b After a 20-mg single oral dose. c CL/F reported. d Study in patients with moderate
to severe renal impairment. e V β
/F reported. f Study in patients with severe renal impairment.
g
Following a single 20-mg oral dose.
Meperidine a
52 ± 3 ~5 (l-25) b 58 ± 9 c 17 ± 5 4.4 ± 0.9 3.2 ± 0.8 d IM: <l e IV: 0.67 μg/mL e
a LD b Aged, RD b AVH, LD, RD, a Aged, Prem a AVH, LD, IM: ~0.7 μg/mL e
Prem, Neo
Prem, Neo,
Aged, RD
i LD i Aged, Preg, Smk i LD, i Preg
Preg, RD
a
Meperidine undergoes cytochrome P450-dependent N-demethylation to normeperidine. The
metabolite is not an analgesic but is a potent central nervous system–excitatory agent and is
associated with adverse side effects of meperidine. b Meperidine is a weak base (pK a
= 8.6)
and is excreted to a greater extent in the urine at low urinary pH and to a lesser extent at high
urinary pH. c Correlates with the concentration of α 1
-acid glycoprotein. d A longer t 1/2
(7 hours)
1000-mg oral dose (SD) and mean following a 250-mg oral dose given once weekly for
4 weeks (MD).
Reference: Karbwang J, et al. Clinical pharmacokinetics of mefloquine. Clin Pharmacokinet,
1990, 19:264–279.
References: Periclou A, et al. Pharmacokinetic study of memantine in healthy and renally
impaired subjects. Clin Pharmacol Ther, 2006, 79:134–143. Periclou AP, et al. Lack of
pharmacokinetic or pharmacodynamic interaction between memantine and donepezil.
Ann Pharmacother, 2004, 38:1389–1394.
also is observed. e Following a continuous 24-mg/hr IV infusion or 100-mg IM injection every
4 hours to steady state. Postoperative analgesia occurs at 0.4-0.7 μg/mL.
Reference: Edwards DJ, et al. Clinical pharmacokinetics of pethidine: 1982. Clin
Pharmacokinet, 1982, 7:421–433.