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

Imipenem/Cilastatin a
Imipenem 69 ± 15 <20 2.9 ± 0.3 0.23 ± 0.05 0.9 ± 0.1 IM: 1-2 b IV: 60-70 μg/mL b
— b Neo, Inflam a Child a Neo, i Neo, IM: 8.2-12 μg/mL b
b RD Child, Prem RD, Prem
i Child, CF i CF, Inflam, i CF, RD, i CF, Child,
Neo, Aged, Aged Aged
Burn, Prem
Cilastatin 70 ± 3 ~35 3.0 ± 0.3 0.20 ± 0.03 0.8 ± 0.1
— b Neo a Child i Neo, RD, a Neo, Prem
CF, Aged
i CF b Neo, RD, Prem a Prem i CF, Aged
i CF, Aged
a
Formulated as a 1:1 (mg/mg) mixture for parenteral administration; cilastatin inhibits the
metabolism of imipenem by the kidney, increasing concentrations of imipenem in the urine;
cilastatin does not change imipenem plasma concentrations appreciably. b Plasma C max
of
imipenem following a single 1-g IV infusion over 30 minutes or 750 mg IM injection.
Indomethacin
~100 15 ± 8 90 1.4 ± 0.2 0.29 ± 0.04 2.4 ± 0.2 a ~1.3 b ~2.4 μg/mL b
i Alb, b Prem, i Aged i RA, RD
Prem, Neo Neo, Aged
a Neo, Prem, Aged
a
Undergoes significant enterohepatic recycling (~50% after an IV dose). b Following a single
50-mg oral dose given after a standard breakfast. Effective at concentrations of 0.3-3 μg/mL
and toxic at >5 μg/mL.
Interferon Alfa a
I-SC: 90 — b — I: 2.8 ± 0.6 c I: 0.40 ± 0.19 c I: 0.67 d I: 7.3 e I: 1.7(1.2-2.3) ng/mL e
PI 12kD
: 0.17 PI 12kD
: 0.44-1.04 PI 12kD
: 37(22-60) PI 12kD
: 22 f
PI 40kD
: 0.014- PI 40kD
: 0.11 PI 40kD
: 65 PI 40kD
: 80 g PI 12kD
: 0.91 ±
0.024 -0.17 0.33 ng/mL f
a
Values for recombinant interferon alfa-2a (I) and its 40-kDa pegylated form (PI 40kD
) and the
12-kDa pegylated form of interferon alfa-2b (PI 12kD
) are reported. b I undergoes renal filtration,
tubular reabsorption, and proteolytic degradation within tubular epithelial cells. Renal elimination
of PI forms is much less significant than that of I, although not negligible. c CL values
in four patients with leukemia were more than halved (1.1 ± 0.3 mL/min/kg), while V ss
increased more than 20-fold (9.5 ± 3.5 L/kg) and terminal t 1/2
changed only minimally (7.3 ±
2.4 hours). d A terminal t 1/2
of 5.1 ± 1.6 hours accounts for 23% of the CL of I. e Following a
single 36 × 10 6 units SC dose of I. f Following 4 weeks of multiple SC dosing of 1 μg/kg of
PI 12kD
. g Following 48 weekly SC doses of 180 μg of PI 40kD
.
Reference: Buckley MM, et al. Imipenem/cilastatin. A reappraisal of its antibacterial activity,
pharmacokinetic properties and therapeutic efficacy. Drugs, 1992, 44:408–444.
Reference: Oberbauer R, et al. Pharmacokinetics of indomethacin in the elderly. Clin
Pharmacokinet, 1993, 24:428–434.
PI 40kD
: 26 ± 8.8 ng/mL g
References: Glue P, et al. Pegylated interferon-2b: Pharmacokinetics, pharmacodynamics,
safety, and preliminary efficacy data. Hepatitis C Intervention Therapy Group. Clin
Pharmacol Ther, 2000, 68:556–567. Harris JM, et al. Pegylation: A novel process for modifying
pharmacokinetics. Clin Pharmacokinet, 2001, 40:539–551. PDR54, 2000, p. 2654. Wills
RJ. Clinical pharmacokinetics of interferons. Clin Pharmacokinet, 1990, 19:390–399.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
1941