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
Pioglitazone a
— Negligible >99 1.2 ± 1.7 b 0.63 ± 0.41 b 11 ± 6 c P: 3.5 (1-4) d P: 1.6 ± 0.2 μg/mL d
a
Data from healthy male and female subjects and patients with type 2 diabetes. Pioglitazone
(P) is metabolized extensively by CYP2C8, CYP3A4, and other CYP isozymes. Two major
metabolites (M-III and M-IV) accumulate in blood and contribute to the pharmacological
effect. b CL/F and V area
/F reported. CL/F is lower in women than in men. c Steady-state t 1/2
of
Posaconazole a
M-III: 11 (2-48) d M-III: 0.4 ± 0.2
μg/mL d
M-IV: 11 (4-16) d M-IV: 1.4 ± 0.5
μg/mL d
— — 98 11.7 ± 6.4 b 11.9 b 21.6 ± 8.4 4 (3-12) 324 ± 161 ng/mL c
i RD i RD i RD i RD
a
~66% of an oral posaconazole dose is excreted unchanged in feces. It is unclear whether this
represents significant biliary excretion or unabsorbed drug. b CL/F and V d
/F reported.
c
Following a single 400-mg dose of an oral suspension.
Pramipexole a
M-III and M-IV is 29 and 27 hours, respectively. d Following a 45-mg oral dose given once
daily for 10 days.
References: Budde K, et al. The pharmacokinetics of pioglitazone in patients with impaired
renal function. Br J Clin Pharmacol, 2003, 55:368–374. PDR58, 2004, p. 3186.
References: Courtney R, et al. Posaconazole pharmacokinetics, safety, and tolerability in
subjects with varying degrees of chronic renal disease. J Clin Pharmacol, 2005, 45:185–192.
Dodds Ashley ES, et al. Pharmacokinetics of posaconazole administered orally or by nasogastric
tube in healthy volunteers. Antimicrob Agents Chemother, 2009, 53:2960–2964.
>90 b ~90 15 8.2 ± 1.4 b 7.3 ± 1.7 b 11.6 ± 2.57 1-2 M: 1.6 ± 0.23 ng/mL e
b Aged, RD, c PD d a Aged, RD F: 2.1 ± 0.25 ng/mL e
a
Data from healthy adult male and female subjects. No significant gender differences.
b
Bioavailability estimated from urinary recovery of unchanged drug. CL/F and V area
/F
reported. c CL/F reduced, moderate to severe renal impairment. d Parkinson’s disease (PD);
CL/F reduced with declining renal function. e Following a 0.5-mg oral dose given three times
daily for 4 days to male (M) and female (F) adults.
References: Lam YW. Clinical pharmacology of dopamine agonists. Pharmacotherapy, 2000,
20:17S–25S. PDR54, 2000, p. 2468. Wright CE, et al. Steady-state pharmacokinetic properties
of pramipexole in healthy volunteers. J Clin Pharmacol, 1997, 37:520–525.