Antiviral Drugs - Drug Design and Discovery - page 397

24.2.1.5 Lamivudine
Structure (Figure 24.1): (−)- β -l-3 ′ -T h ia-2 ′ ,3 ′ -dideoxycytidine (3TC), Epivir ® (for HIV), Zefi x ®

(for HBV).
Activity spectrum : HIV (types 1 and 2) and HBV.
Mechanism of action : Targeted at HIV RT and HBV RT, acts as chain terminator, following
intracellular phosphorylation to 3TC 5 ′ -triphosphate, and, after removal of the diphosphate group,

-end of the viral DNA chain.
Principal indication(s) : HIV and HBV infections: for HIV infection, in combination with other
anti-HIV agents (such as zidovudine and abacavir).
Administered : Orally at 300 mg/day (one 150 mg tablet twice a day, or one 300 mg tablet once
a day). In the treatment of HIV infections, lamivudine can be combined with zidovudine
(Combivir ® ), or with zidovudine and abacavir (Trizivir ® ). Combivir tablets contain 300 mg zido-
vudine and 150 mg lamivudine per tablet and are administered orally (two tablets daily). Trizivir
tablets contain 300 mg zidovudine, 150 mg lamivudine, and 300 mg abacavir per tablet and are
administered orally (two tablets daily). Lamivudine is administered orally at 100 mg/day in the
treatment of HBV infections.

incorporation of 3TC 5 ′ -monophosphate at the 3 ′

24.2.1.6 Abacavir
Structure (Figure 24.1): (1 S ,4 R )-4-[2-Amino-6-(cyclopropylamino)-9 H -purin-9-yl]-2-cyclopentene-
1-methanol succinate (ABC), Ziagen ® .
Activity spectrum : HIV (types 1 and 2).
Mechanism of action : Targeted at HIV RT, acts as chain terminator, following intracellular phos-
phorylation and conversion (deamination) to the 5

-triphosphate of the corresponding guanosine
analog (carbovir), and, after removal of the diphosphate group, incorporation of carbovir 5

′

′ -mono-

phosphate at the 3 -end of the viral DNA chain.

Principal indication(s) : HIV infection, in combination with other anti-HIV agents such as zidovu-
dine and lamivudine (see above).
Administered : Orally at 600 mg/day (two 300 mg tablets daily).

′

24.2.1.7 Emtricitabine
Structure (Figure 24.1): (−)-

β -l-3 ′ -T h ia-2 ′ ,3 ′ -dideoxy-5-l uorocytidine, [(−)-FTC], Emtriva ® .

Activity spectrum : HIV and HBV.
Mechanism of action : Similar to that of 3TC.
Principal indication(s) : HIV infections, where it is used in combination with tenofovir disoproxil
fumarate (TDF) as a single tablet to be taken orally once daily.
Administered : Orally as a once-daily 200 mg capsule containing only emtricitabine or as a once-
daily tablet containing 200 mg emtricitabine and 300 mg TDF (Truvada ® ).

24.2.2 N UCLEOTIDE R EVERSE T RANSCRIPTASE I NHIBITORS (N T RTI S )

24.2.2.1 Tenofovir Disoproxil
Structure (Figure 24.1): Fumarate salt of bis(isopropoxycarbonyloxymethyl) ester of ( R )-9-(2-
phosphonylmethoxypropyl)adenine, or bis(POC)PMPA, Viread ® .
Activity spectrum : HIV (types 1 and 2) and various other retroviruses, and HBV.
Mechanism of action : Serves as oral prodrug of tenofovir (PMPA) that is targeted at HIV RT (and
HBV RT), and acts as chain terminator, following intracellular phosphorylation to the diphosphate