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
Daptomycin
— a 47 ± 12 92 0.14 ± 0.01 0.096 ± 0.009 7.8 ± 1.0 — 99 ± 12 μg/mL c
a RD b a RD b a RD b
a
Available for IV administration only. b Changes reported for patients with severe renal impairment.
c C max
at the end of a 30-minute IV infusion of a 6-mg/kg dose given once daily for
7 days. No significant accumulation with multiple dosing.
Darunavir a
82 — 95 1.4 ± 0.5 1.9 15 (13-21) 2.5-4 e 11-15 μg/mL e
a Food b
i LD c
i RD d
a
Darunavir should be taken in combination with ritonavir, a potent CYP3A and P-glycoprotein
inhibitor, which profoundly increases systemic exposure to darunavir. Data reported are for combined
administration of darunavir (IV or oral) with 100-mg oral ritonavir, twice daily. b Systemic
exposure increased 42% when taken with a meal. c Study in patients with mild to moderate liver
impairment. d Study in patients with moderate renal impairment. e Following 600-mg darunavir
once daily and 100-mg ritonavir twice daily, to steady state; C trough
= 3.5 (1.6-7.4) μg/mL.
Dextroamphetamine a
— b Rac: 14.5 c Rac: 23-26 Dextro: 3.4-7.7 d Rac: 6.11 ± 0.22 Rac: 3.5-4.2 d Dextro: Dextro: 61 ±
(Acidic urine) (Acidic urine) 3.1 ± 1.1 f 20 ng/mL f
Dextro: 0.23-1.71 d
Rac: 14-22 d
(Alkaline urine)
a
Amphetamine is available as a racemate (Rac), dextro-isomer (Dextro), and a mixture of the
two, in both immediate- and extended-release formulations. Pharmacokinetic data on both
racemic and dextroamphetamine are presented. b Absolute bioavailability not reported; >55%
based on urine recovery of unchanged drug under acidic urinary pH conditions. c Measured
under uncontrolled urinary pH condition. Renal CL of amphetamine is dependent on urine
pH. Acidification of urine results in increased urinary excretion, up to 55%. d CL/F and t 1/2
following oral dose to adults is reported. e t 1/2
in children reported. f Following a 20-mg
immediate-release oral dose given once daily for >1 week. An extended-release formulation
References: Dvorchik BH, et al. Daptomycin pharmacokinetics and safety following administration
of escalating doses once daily to healthy subjects. Antimicrob Agents Chemother, 2003,
47:1318–1323. Product information: Cubicin TM (daptomycin for injection). Lexington, MA,
Cubist Pharmaceuticals, 2004.
References: Drugs @FDA. Prezista label approved on 6/16/09. Available at: http://www.
accessdata.fda.gov/drugsatfda_docs/label/2009/021976s010lbl.pdf. Accessed May 17, 2010.
McCoy C. Darunavir: A nonpeptidic antiretroviral protease inhibitor. Clin Ther, 2007,
29:1559–1576. Rittweger M, et al. Clinical pharmacokinetics of darunavir. Clin
Pharmacokinet, 2007, 46:739–756.
(Alkaline urine)
Dextro: 6.8 ± 0.5 e
(Uncontrolled urine
pH)
consisting of a mixture of dextroamphetamine and amphetamine salts (ADDERALL XR) exhibits
a delayed T max
of ~7 hours.
References: Busto U, et al. Clinical pharmacokinetics of non-opiate abused drugs. Clin
Pharmacokinet, 1989, 16:1–26. Helligrel ET, et al. Steady-state pharmacokinetics and tolerability
of modafinil administered alone or in combination with dextroamphetamine in healthy
volunteers. J Clin Pharmacol, 2002, 42:450–460. McGough JJ, et al. Pharmacokinetics of
SLI381 (ADDERALL XR), an extended-release formulation of Adderall. J Am Acad Child
Adolesc Psychiatry, 2003, 42:684–691.