Antiviral Drugs - Drug Design and Discovery - page 400

Principal indication(s) : HIV-1 infection, in combination with other anti-HIV agents, particularly
NRTIs.
Administered : Orally at 200 mg/day for the i rst 14 days (one 200 mg tablet per day), then 400 mg/day
(two daily 200 mg tablets).
24.2.3.2 Delavirdine
Structure (Figure 24.4): 1-(5-Methanesulfonamido-1 H -indol-2-yl-carbonyl)-4-[3-(1-methylethyl-
amino)pyridinyl)piperazine monomethane sulfonate, Rescriptor ® .
Activity spectrum : HIV type 1.
Mechanism of action : Similar to that of nevirapine.
Principal indication(s) : HIV-1 infection, in combination with other anti-HIV agents (primarily
NRTIs).
Administered : Orally at 1200 mg/day (two 200 mg tablets three times a day).
24.2.3.3 Efavirenz
Structure (Figure 24.4): (−)6-Chloro-4-cyclopropylethynyl-4-tril uoromethyl-1,4-dihydro-2 H -
3,1-benzoxazin-2-one, Sustiva ® , Stocrin ® .
Activity spectrum : HIV type 1.
Mechanism of action : Similar to that of nevirapine.
Principal indication(s) : HIV-1 infection, in combination with other anti-HIV agents, particularly
TDF and emtricitabine (see above).
Administered : Orally once-daily at 600mg/day, as 600mg tablet, preferably at bedtime to
improve tolerability of CNS side effects, or, in combination with TDF and emtricitabine (Atripla)
(see above).
24.2.4 P ROTEASE I NHIBITORS (PI S )
24.2.4.1 Saquinavir
Structure (Figure 24.6): cis - N - tert -Butyl-decahydro-2-[2( R )-hydroxy-4-phenyl-3( S )-[[ N -2-
quinolylcarbonyl-l-asparaginyl]-amino]butyl]-(4a S -8a S )-isoquinoline-3( S )-carboxamide methane
sulfonate, hard gel capsules, Invirase ® , also available as soft gelatin capsules (Fortovase ® ).
Activity spectrum : HIV (types 1 and 2).
Mechanism of action : Transition-state, hydroxyethylene-based, peptidomimetic inhibitor of HIV
protease (as illustrated for Darunavir (see below) in Figure 24.7).
Principal indication(s) : HIV infection, in combination with other anti-HIV agents (i.e., NRTIs) or
ritonavir as “booster.”
Administered : Orally at 3600 mg/day (six 200 mg soft gelatin capsules three times a day (Fortovase))
or 1800 mg/day (three 200 mg hard gel capsules three times a day (Invirase)), to be taken with a
meal or up to 2 h after a full meal. If boosted with ritonavir, 1000 mg saquinavir/100 mg ritonavir
twice daily.
24.2.4.2 Ritonavir
Structure (Figure 24.6): [5 S -(5 R ,8 R ,10 R ,11 R )]-10-Hydroxy-2-methyl-5-(1-methylethyl)-1-[2-(methylethyl)-
4-thiazolyl]-3,6-dioxo-8,11-bis(phenylmethyl)-2,4,7,12-tetraazatridecan-13-oic acid 5-thiazolylmethyl
ester, Norvir ® .
Activity spectrum : HIV (types 1 and 2).
Mechanism of action : Peptidomimetic inhibitor of HIV protease.