Biology Reference
In-Depth Information
Table 4.6
Variable Cure Rates of Primaquine against Relapse of M strain of
P. cynomolgi
in Rhesus Macaques when Co-administered with Quinine vs. Chloroquine
Daily primaquine dose
(mg/kg) × 7 days
Blood schizontocide
Number of monkeys
% relapse
None
Quinine
83
98
None
Chloroquine
46
100
0.75
None
38
61
0.75
Quinine
55
45
0.75
Chloroquine
16
25
1.5
None
20
35
1.5
Quinine
5
13
1.5
Chloroquine
5
0
Adapted from
Schmidt (1981)
Table 4.7
Variable Cure Rates of Primaquine against Relapse of B strain of
P. cynomolgi
in Rhesus Macaques when Co-administered with Quinine versus Chloroquine
Daily primaquine
dose (mg/kg) × 7
days
Blood
schizontocide
Number of
monkeys
% relapse
None
Quinine
2
100
None
Chloroquine
2
100
0.38
Quinine
4
100
0.38
Chloroquine
4
75
0.75
Quinine
8
38
0.75
Chloroquine
8
0
1.5
Quinine
4
0
1.5
Chloroquine
4
0
Adapted from
Schmidt (1981)
(
Schmidt, 1981
). Similarly, quinine synergized primaquine against relapse
in this model (
Schmidt et al., 1982
). That laboratory also later reported
screening 265 chemically diverse compounds, finding broad activity at tol-
erable doses only among 8-aminoquinolines (
Schmidt, 1983
). That screen-
ing of compounds and another sponsored by the US Army led to survey of
200 8-aminoquinoline compounds for anti-relapse activity in that model.
That work led to discovery of the drug tafenoquine (30 years later in
phase IIb trials in 2012) (
Davidson et al., 1981
). Schmidt later reported
enhancement of primaquine activity against
P. cynomolgi
relapse by the
concurrent administration of mirinamycin (a lincosamide class antibi-
otic) (
Schmidt, 1985
). This work aimed at reducing the effective doses of
8-aminoquinoline therapy against hypnozoites, so that '…
radical cure might