Cycloguanil pamoate

Lipophilic groups that are not easily hydrolyzed are used extensively for depot preparations, which liberate the active drug molecule slowly, for a period of days or weeks. Steroid hormone palmitates and pamoates, and antimalarial esters (e.g., cycloguanil pamoate, 3.29), can deliver the active drugs over a prolonged time cycloguanil, for example, is released over a period of several months. This can he a great convenience for the patient, especially in areas with remote medical facilities. 

The first drug designed as a repository antimalarial was the pamoate salt of the active metabolite of proguanil, l-(4-chlorophenyl)-4,6-diamino-l,2-dihydro-2,2-dimethyl-j-triazine pamoate (cycloguanil pamoate or embonate, Camolar, CI-501, 37), single intramuscular doses of which protected mice for weeks against blood-induced infections with P. berghei [174] and monkeys... 

These studies culminated in the selection of cycloguanil pamoate (Camolar , CI-501) (XIX) [72] for expanded studies [5]. Cycloguanil pamoate has been subjected to extensive antimalarial and tolerance studies in experimental animals... 

A fourth study was designed to determine whether cycloguanil pamoate might be stored elsewhere after release from the injection site and then released from the second site in sufficient quantity for activity against malarial para-... 

Dialysis studies with cycloguanil pamoate in rats. 

In a similar study in two monkeys, cycloguanil pamoate suspended in BBCO was implanted subcutaneously in dialysis sacks at a dose of 50 mg/kg [45]. When challenged with P. cynomolgi trophozoites 21 days later, both monkeys failed to develop patent infections or to yield positive subinoculations. The drug sack was removed from one monkey on day 49 and both were rechallenged on day 52. Typical acute infections developed in the monkey without the drug sack, but protection persisted in the monkey with the sack still implanted. These results confirm the rat studies summarized previously. 

In human volunteers, a single 5 mg/kg intramuscular dose of cycloguanil pamoate afforded protection for 8 to more than 12 months against subsequent challenges with susceptible strains of P. vivax [75-77] or P. falciparum [78]. 

Cycloguanil pamoate emerges, therefore, as a drug that provides low dihydrotriazine blood levels in much the same manner as might be achieved by an extremely slow intravenous infusion of a soluble salt. One of the most... 

Human malaria parasites vary greatly in sensitivity to sulf ones P. falciparum is very sensitive while P. vivax is not. Therefore, DADDS alone has not been studied extensively in human malaria. In 4 nonimmune human volunteers, a 3.25 mg/kg intramuscular dose of DADDS afforded complete to partial protection against challenges with multiresistant P. falciparum sporozoites through 42 days, while cycloguanil pamoate under the same conditions was ineffective [95]. 

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