Treatment of experimental cryptococcal meningitis and disseminated candidiasis with SCH39304.
We studied the pharmacokinetics and in vivo antifungal action of SCH39304, a new antifungal azole compound, in rabbits. It crossed the blood-cerebrospinal fluid barrier in the presence or absence of meningeal inflammation, reaching approximately 60% of the simultaneous concentrations in serum. In the treatment of experimental cryptococcal meningitis, SCH39304 was as effective as fluconazole in reducing yeast counts in the subarachnoid space. SCH39304 and fluconazole both were highly effective against candida endophthalmitis, sterilizing the vitreous humor and the choroid and retina. SCH39304 suppressed candida endocarditis and reduced yeast counts in the kidney at all doses tested. SCH39304 was effective in the treatment of experimental cryptococcal meningitis and disseminated candidiasis. Further investigations in humans are warranted.
Perfect
J R
JR
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Wright
K A
KA
Hobbs
M M
MM
Durack
D T
DT
D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D003453:Cryptococcosis / Q000188:drug therapy* / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000187:drug effects; D015725:Fluconazole / Q000627:therapeutic use; D008581:Meningitis / Q000188:drug therapy* / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D014230:Triazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000935:Antifungal Agents; D014230:Triazoles; C056513:Sch 39304; D015725:Fluconazole