Pharmacokinetics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, after i.v. bolus multiple administration in rats.
We investigated the pharmacokinetics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, after intravenous (i.v.) bolus administration at a multiple dose every 24 h for 5 days in rats. To analyze ID-6105 levels in biological samples, we used an HPLC-based method which was validated in a pharmacokinetic study by suitable criteria. The concentrations of ID-6105 after the multiple administration for 5 days were not significantly different from the results after the single administration. The t1/2alpha, t1/2beta, Vdss, and CLt after the multiple administration were not significantly different from the values after the single administration. Moreover, the concentrations of ID-6105 1 min at day 1-5 after i.v. bolus multiple administration did not show the significant difference. Of the various tissues, ID-6105 mainly distributed to the kidney, lung, spleen, adrenal gland, and liver after i.v. bolus multiple administration. ID-6105 concentrations in the kidney or lung 2 h after i.v. bolus administration were comparable to the plasma concentration shortly after i.v. bolus administration. However, the ID-6105 concentrations in various tissues 48 h after i.v. bolus administration decreased to low levels. ID-6105 was excreted largely in the bile after i.v. bolus multiple administration at the dose of 3 mg/kg. The amounts of ID-6105 found in the bile by 12 h or in the urine by 48 h after the administration were calculated to be 14.1% or 4.55% of the initial dose, respectively, indicating that ID-6105 is mostly excreted in the bile. In conclusion, ID-6105 was rapidly cleared from the blood and transferred to tissues, suggesting that ID-6105 might not be accumulated in the blood following i.v. bolus multiple dosages of 3 mg/kg every 24 h for 5 days. By 48 h after i.v. bolus administration, ID-6105 concentrations in various tissues had decreased to very low levels. The majority of ID-6105 appears to be excreted in the bile.
Yoo
Bo-Im
BI
National Research Laboratory (NRL) of PK/PD, Biotechnology Research Institute, College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, Korea.
Ahan
Kwang Bok
KB
Kang
Min Hee
MH
Kwon
Oh-Seung
OS
Hong
Young-Soo
YS
Lee
Jung Joon
JJ
Lee
Hong Sub
HS
Ryu
Jung Su
JS
Kim
Tae Yong
TY
Moon
Dong-Cheul
DC
Song
Sukgil
S
Chung
Youn Bok
YB
D015250:Aclarubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004334:Drug Administration Schedule; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
C099664:11-hydroxyaclacinomycin X; D000903:Antibiotics, Antineoplastic; D015250:Aclarubicin