Interspecies comparison of the oral absorption of itraconazole in laboratory animals.
The oral absorption and disposition of itraconazole were studied in rats, rabbits and dogs. Serum levels of itraconazole and its active metabolite, hydroxyitraconazole, were determined by a validated HPLC method. The absorption of itraconazole was relatively rapid in rats and dogs but was slower in rabbits. The terminal elimination half-life (T 1/2lambda(z)), time to the peak concentration (Tmax), dose and weight normalized area under the curve (AUC) and the peak concentration (Cmax) of itraconazole found in the dog were comparable to those reported in humans. As in humans, the metabolite to parent drug AUC ratios in rats and dogs were greater than unity but was less in rabbits. The dog appears to be an appropriate animal model while the rat, not the rabbit, may be used as an alternative animal model in predicting the oral absorption of itraconazole in humans.
Yoo
Sun Dong
SD
College of Pharmacy, Sungkyunkwan University, Suwon, Kyonggi-do, Korea. sdyoo@skku.ac.kr
Kang
Eunhee
E
Shin
Beom Soo
BS
Jun
Hun
H
Lee
Sang-Heon
SH
Lee
Kang Choon
KC
Lee
Kyu-Hyun
KH
D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004285:Dogs; D006207:Half-Life; D006900:Hydroxylation; D007408:Intestinal Absorption; D017964:Itraconazole / Q000493:pharmacokinetics*; D008297:Male; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D000935:Antifungal Agents; D017964:Itraconazole