Charles Bowesman, O.B.E., B.A., M.D., F.R.C.S.E., F.A.C.S., D.T.M.&H., Editor. 1st edition, 1068 + viii pages, illustrated. Edinburgh and London, E. & S. Livingstone Ltd. (The Williams & Wilkins Co., Baltimore, exclusive U.S. agents), 1960. $22.50
In a continuing effort to develop repository antimalarials that would be effective against both normal and drug-resistant parasites, 4,4′-diacetylaminodiphenylsulfone (DADDS) was studied alone and mixed with cycloguanil pamoate. Trophozoite-induced infections of Plasmodium berghei and of P. cynomolgi were used in mice and rhesus monkeys. The drugs were given subcutaneously to mice and intramuscularly to monkeys, as either aqueous or lipid suspensions.
DADDS had varying degrees of prolonged action in mice: a dose of 100 to 400 mg/kg almost invariably prevented or greatly suppressed patent infections through 6 to 14 weeks.
A 50 mg/kg dose of DADDS prevented patent infections in monkeys for 63–268 (average 158) days and greatly suppressed the parasitemia for many weeks longer.
In therapeutic tests against established patent infections in monkeys, DADDS suppressed the parasitemia slowly.
There were indications that DADDS was slowly released from the injection site and led to low blood levels of active moiety over prolonged periods. The drug was well tolerated locally and systemically by gross examination.
In the prevention of patent infections in monkeys, DADDS and cycloguanil pamoate (of comparable particle sizes) protected for similar periods of time and a 1:1 mixture protected as long as an equivalent amount of either drug alone.
DADDS, cycloguanil pamoate, and a 1:1 mixture were compared against lines of P. berghei highly resistant to either diaminodiphenylsulfone or to the dihydrotriazine moiety of cycloguanil pamoate. The mixture had broader repository action against the drug-resistant lines than did either drug alone.