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

Trimethoprim
>63 63 ± 10 37 ± 5 1.9 ± 0.3 a 1.6 ± 0.2 a 10 ± 2 a 2 b 1.2 μg/mL b
i CF i RD, b RD i RD, CF a RD
Alb, CF a CF, Child a Neo, Child b Child, CF
a
Studies included concurrent administration of sulfamethoxazole and variation in urinary pH;
these factors had no marked effect on the CL, V area
, and t 1/2
of trimethoprim. b Following a single
160-mg oral dose given to healthy adults.
Valacyclovir a
V: very low V: <1 V: 13.5-17.9 V: — — V: — V: 1.5 V: ≤0.56 μg/mL e
A: 54 (42-73) b A: 44 ± 10 c A: 22-33 A: b RD d A: 2.5 ± 0.3 A: 1.9 ± 0.6 e A: 4.8 ± 1.5 μg/mL e
a
Data from healthy male and female adults. Valacyclovir is an L-valine prodrug of acyclovir.
Extensive first-pass conversion by intestinal (gut wall and luminal) and hepatic enzymes.
Parameters refer to acyclovir (A) and valacyclovir (V) following V administration. See
“Acyclovir” for its systemic disposition parameters. b Bioavailability of A based on AUC of A
following IV A and a 1-g oral dose of V. c Urinary recovery of A is dose dependent (76% and
44% following 100-mg and 1000-mg oral doses of V, and 87% following IV A). d CL/F
reduced, end-stage RD (drug cleared by hemodialysis). e Following a single 1-g oral dose of V.
Valganciclovir a
References: Hutabarat RM, et al. Disposition of drugs in cystic fibrosis. I. Sulfamethoxazole
and trimethoprim. Clin Pharmacol Ther, 1991, 49:402–409. Welling PO, et al.
Pharmacokinetics of trimethoprim and sulfamethoxazole in normal subjects and in
patients with renal failure. J Infect Dis, 1973, 128(suppl):556–566.
A: a RD
G (V): 61 ± 9 b — — — — V (V): 0.5 ± 0.2 V (V): 0.5 ± V (V): 0.20 ±
0.3 d 0.07 μg/mL d
a Food G (V): 3.7 ± 0.6 G (V): l-3 e G (V): 5.6 ±
a RD c
1.5 μg/mL e
a
Valganciclovir (V) is an ester prodrug for ganciclovir (G). It is rapidly hydrolyzed with a
plasma t 1/2
= 0.5 hour. G and V data following oral V dosing to male and female patients with
viral infections are reported. See “Ganciclovir” for its systemic disposition parameters.
b
lncreased and more predictable bioavailability of G when V is taken with a high-fat meal.
c
The apparent t 1/2
of G is increased in patients with renal impairment. d Following a single
360-mg oral dose of V taken without food. e Following a 900-mg oral dose of V taken once
daily with food to steady state.
References: Perry CM, et al. Valaciclovir. A review of its antiviral activity, pharmacokinetic
properties and therapeutic efficacy in herpesvirus infections. Drugs, 1996, 52:754–772. Soul-
Lawton J, et al. Absolute bioavailability and metabolic disposition of valaciclovir, the L-valyl
ester of acyclovir, following oral administration to humans. Antimicrob Agents Chemother,
1995, 39:2759–2764. Weller S, et al. Pharmacokinetics of the acyclovir pro-drug valaciclovir
after escalating single- and multiple-dose administration to normal volunteers. Clin
Pharmacol Ther, 1993, 54:595–605.
References: Cocohoba JM, et al. Valganciclovir: An advance in cytomegalovirus therapeutics.
Ann Pharmacother, 2002, 36:1075–1079. Jung D, et al. Single-dose pharmacokinetics of valganciclovir
in HIV- and CMV-seropositive subjects. J Clin Pharmacol, 1999, 39:800–804.
PDR58, 2004, pp. 2895, 2971.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
1985