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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
 
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