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WR 33063, a phenanthrene methanol, was studied in human volunteers for tolerance and toxicity. In normal volunteers, it was possible to give 4.6 g in four divided doses without adverse effect for 10 days. At this dose level, there was neither evidence of photosensitivity nor adverse renal or cardiac effect. At a dose level of 1.6 g in four divided doses for 6 days, WR 33063 cured 18 of 23 nonimmune volunteers infected with the Smith strain of Plasmodium falciparum from Vietnam. In addition, infections due to the Marks and Braithwaite Vietnam strains were also treated because these strains represent a major therapeutic challenge to chloroquine; six of six and two of three volunteers, respectively, were cured. With the Malayan Camp strain, 1.6 g in four divided doses for 6 days cured all of five volunteers. The African Uganda I strain of chloroquine-responsive malaria was even more responsive to WR 33063; all of six men who received 1.6 g in four divided doses for 6 days were cured, and all of three men who received this same dosage for 3 days were cured. One subject infected with a Haitian strain of P. falciparum was treated and cured. Blood-induced infections with the Chesson strain of P. vivax also responded well to WR 33063 with four of five men cured. In all, 52 men received WR 33063 in tolerance trials, and 59 men with experimental malaria and one man with clinical malaria were treated with WR 33063.

WR 30090 at a dose of 230 mg every 8 hr for 6 days has proven to be a safe, well-tolerated compound with photosensitivity proving to be a minor consideration. WR 30090 was found to be an effective medication for the treatment of acute malaria caused by several strains of Plasmodium falciparum. At the dose of 230 mg every 8 hr for 6 days, all of six men infected with a chloroquine-susceptible strain (Uganda I) were cured, all of 13 subjects infected with moderately chloroquine-resistant strains (Malayan Camp, Malayan Taylor, and Philippine Per) were cured, and 19 of 23 subjects infected with strains highly resistant to chloroquine (Vietnam Smith and Vietnam Crocker) were cured. All of five subjects infected with the chloroquine-resistant Vietnam Marks strain were cured with only 3 days of therapy. Blood-induced P. vivax (Chesson strain) infection showed a mixed response. Six out of seven volunteers were cured when treated for 3 days with WR 30090. The one recrudescence responded to a repeated course of therapy for 3 days. However, recrudescence occurred in one volunteer treated for 6 days. Treatment with WR 30090 failed to cure sporozoite-induced P. vivax (Chesson strain) infection in any of four subjects. In all subjects treated, there was good suppression of parasitemia and relief of symptoms. The susceptibility of the strains of malaria to WR 30090 to some degree parallels their susceptibility to chloroquine.