Comparative toxicities and pharmacokinetics of intrathecal lipid (amphotericin B colloidal dispersion) and conventional deoxycholate formulations of amphotericin B in rabbits.
The lipid formulation of amphotericin B, Amphotec (ABCD), has not been used intrathecally. After a single intrathecal dose or after four doses, conventionally formulated deoxycholate amphotericin B (AMB) (Fungizone) resulted in higher levels of amphotericin B in the cerebrospinal fluid of rabbits than did ABCD. Clinically and histologically, ABCD was about threefold less toxic than AMB after a single dose and 3- to 30-fold less toxic after multiple dosing. These data are encouraging for the potential use of ABCD as an intrathecal treatment.
Clemons
K V
KV
California Institute for Medical Research, Division of Infectious Diseases, Santa Clara Valley Medical Center, San Jose, California 95128, USA. Karl.Clemons@slip.net
Sobel
R A
RA
Williams
P L
PL
Stevens
D A
DA
D000666:Amphotericin B / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000633:toxicity*; D000818:Animals; D000935:Antifungal Agents / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000633:toxicity*; D001681:Biological Assay; D001921:Brain / Q000473:pathology; D007278:Injections, Spinal; D008297:Male; D010143:Paecilomyces / Q000187:drug effects; D011817:Rabbits; D013116:Spinal Cord / Q000473:pathology
D000935:Antifungal Agents; D000666:Amphotericin B