Pharmacokinetics of albendazole in New Zealand white rabbits: oral versus intraperitoneal administration.
BACKGROUND
Recent studies from our group have shown the potent antitumor effects of albendazole (ABZ). It was hypothesized that intraperitoneal (i.p.) administration of ABZ in peritoneal carcinomatosis (PC) could lead to long exposure of tumor cells to high concentration of the drug and possibly to reduced systemic toxicity.


METHODS
Eight male New Zealand white rabbits were randomized into two groups, all given a single dose of ABZ 150 mg/kg suspended in 0.5% carboxymethylcellulose (CMC), either as i.p. injection, or as oral administration. The concentration of ABZ and its metabolites in plasma were determined using a high performance liquid chromatography method.


RESULTS
The parent drug was detected in plasma after oral and i.p. administration. The C(max) of albendazole sulphoxide (ABZ-SO) resulted in a much higher plasma concentration in the oral group (41.86 microg/ml) than in the i.p. group (16.84 microg/ml, p < 0.05). The area under the concentration over time curve of ABZ-SO in the oral group (1010.43 microg/ml/h) was also significantly higher than that of the i.p. group (528.33 microg/ml/h, p < 0.05). Compared to oral administration, the i.p. administration of an ABZ suspension led to significantly lower plasma levels of the major metabolite (ABZ-SO). This could have considerable therapeutic benefits in the regional treatment of PC.
Cai
Zhao-Yan
ZY
Department of Surgery, The University of New South Wales, St. George Hospital, Kogarah, Sydney, NSW 2217, Australia.
Galettis
Peter
P
Lu
Ying
Y
Morris
David L
DL
Pourgholami
Mohammad H
MH
D000284:Administration, Oral; D015766:Albendazole / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007274:Injections, Intraperitoneal; D008297:Male; D011817:Rabbits; D011897:Random Allocation
D000970:Antineoplastic Agents; D015766:Albendazole; C027186:albendazole sulfoxide