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
Chlorpromazine a
32 ± 19 b <1 95-98 8.6 ± 2.9 c 21 ± 9 c 30 ± 7 c 1-4 d 25-150 ng/mL d
i RD b Child
i LD
a
Active metabolites, 7-hydroxychlorpromazine (t 1/2
= 25 ± 15 hours) and possibly chlorpromazine
N-oxide, yield AUCs comparable to the parent drug (single doses). b After a single
dose. Bioavailability may decrease to ~20% with repeated dosing. c CL/F, V area
, and terminal
t 1/2
following IM administration. d Following a 100-mg oral dose given twice a day for 33 days
Chlorthalidone
64 ± 10 65 ± 9 a 75 ± 1 0.04 ± 0.01 0.14 ± 0.07 47 ± 22 b 13.8 ± 6.3 c 3.7 ± 0.9 μg/mL c
b Aged
a Aged
a
Value is for 50- and 100-mg doses; renal CL is decreased at an oral dose of 200 mg, and there
is a concomitant decrease in the percentage excreted unchanged. b Chlorthalidone is
sequestered in erythrocytes. t 1/2
is longer if blood, rather than plasma, is analyzed. Parameters
reported based on blood concentrations. c Following a single 50-mg oral dose (tablet) given to
healthy male adults.
Cidofovir a
to adult patients. Neurotoxicity (tremors and convulsions) occurs at concentrations of 750-
1000 ng/mL.
Reference: Dahl SG, et al. Pharmacokinetics of chlorpromazine after single and chronic
dosage. Clin Pharmacol Ther, 1977, 21:437–448.
Reference: Williams RL, et al. Relative bioavailability of chlorthalidone in humans: Adverse
influence of polyethylene glycol. J Pharm Sci, 1982, 71:533–535.
SC: 98 ± 10 70.1 ± 21.4 b <6 2.1 ± 0.6 b 0.36 ± 0.13 b 2.3 ± 0.5 b — 19.6 ± 7.2 μg/mL d
PO: <5 b RD c a RD
a
Data from patients with HIV infection and positive for cytomegalovirus. Cidofovir is activated
intracellularly by phosphokinases. For parenteral use. b Parameters reported for a dose
given in the presence of probenecid. c CL reduced, mild renal impairment (cleared by highflux
hemodialysis). d Following a single 5-mg/kg IV infusion given over 1 hour, with
concomitant oral probenecid and active hydration.
References: Brody SR, et al. Pharmacokinetics of cidofovir in renal insufficiency and in continuous
ambulatory peritoneal dialysis or high-flux hemodialysis. Clin Pharmacol Ther, 1999,
65:21–28. Cundy KC, et al. Clinical pharmacokinetics of cidofovir in human immunodeficiency
virus-infected patients. Antimicrob Agents Chemother, 1995, 39:1247–1252. PDR54, 2000, p.
1136. Wachsman M, et al. Pharmacokinetics, safety and bioavailability of HPMPC (cidofovir) in
human immunodeficiency virus-infected subjects. Antiviral Res, 1996, 29:153–161.