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

Table 59–4
Pharmacokinetic Properties of HIV-1 Protease Inhibitors a
PARAMETER SAQUINAVIR b INDINAVIR RITONAVIR NELFINAVIR FOSAMPRENAVIR LOPINAVIR c ATAZANAVIR TIPRANAVIR DARUNAVIR
Oral 13 60-65 >60 20-80 (formu- ND ND ND ND 82
bioavailability, %
lation- and
fooddependent)
Effect of meals a570% b77% a13% a100–200% i a27% a70% i a30%
on AUC (high fat) (high fat) (capsule) (moderate fat) (light meal)
Plasma t 1/2
, h 1-2 1.8 3-5 3.5-5 7.7 5-6 6.5-7.9 4.8-6.0 15
Plasma protein 98 60 98-99 >98 90 98-99 86 99.9 95
binding, %
Metabolism CYP3A4 CYP3A4 CYP3A4 > CYP2C19 > CYP3A4 CYP3A4 CYP3A4 CYP3A4 CYP3A4
CYP2D6 CYP3A4
Autoinduction No No Yes Yes No Yes No Yes ND
of metabolism
Renal excretion <3 9-12 3.5 1-2 1 <3 7 0.5 8
of parent
drug, %
Inhibition of + ++ +++ ++ ++ +++ ++ +++ +++
CYP3A4
ABBREVIATIONS: AUC area under plasma concentration–time curve; t 1/2
half-life of elimination; a, increase; b, decrease; i, no effect; CYP, cytochrome P450; ND, not determined; +, weak;
++, moderate; +++, substantial. a Reported mean values in adults with normal renal and hepatic function. b Parameters reported for the saquinavir soft-gel capsule formulation. c Values for lopinavir,
tipranavir, and darunavir reflect coadministration with ritonavir.
CHAPTER 59
ANTIRETROVIRAL AGENTS AND TREATMENT OF HIV INFECTION
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