Pharmacokinetics of Guanosine in Rats following Intravenous or Intramuscular Administration of a 1:1 Mixture of Guanosine and Acriflavine, a Potential Antitumor Agent

Shin, Dae-Hwan; Choi, Kyu-Seok; Cho, Byung-Suk; Song, Suk-Gil; Moon, Dong-Cheul; Hong, Jin-Tae; Lee, Chong-Kil; Chung, Youn-Bok

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자료유형: 학술저널

저자정보: Shin, Dae-Hwan (National Research Laboratory [NRL] of PK/PD, CBITRC, Biotechnology Research Institute, College of Pharmacy, Chung-buk National University) Choi, Kyu-Seok (National Research Laboratory [NRL] of PK/PD, CBITRC, Biotechnology Research Institute, College of Pharmacy, Chung-buk National University) Cho, Byung-Suk (National Research Laboratory [NRL] of PK/PD, CBITRC, Biotechnology Research Institute, College of Pharmacy, Chung-buk National University) Song, Suk-Gil (National Research Laboratory [NRL] of PK/PD, CBITRC, Biotechnology Research Institute, College of Pharmacy, Chung-buk National University) Moon, Dong-Cheul (National Research Laboratory [NRL] of PK/PD, CBITRC, Biotechnology Research Institute, College of Pharmacy, Chung-buk National University) Hong, Jin-Tae (National Research Laboratory [NRL] of PK/PD, CBITRC, Biotechnology Research Institute, College of Pharmacy, Chung-buk National University) Lee, Chong-Kil (National Research Laboratory [NRL] of PK/PD, CBITRC, Biotechnology Research Institute, College of Pharmacy, Chung-buk National University) Chung, Youn-Bok (National Research La)

저널정보: 대한약학회 Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea 제31권 제10호

발행연도: 2008.1

수록면: 1,347 - 1,353 (7page)

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A 1:1 mixture of acriflavine (ACF; CAS 8063-24-9) and guanosine is under evaluation in preclinical studies as a possible antitumor agent. Guanosine is known to potentiate the anti-cancer activity of ACF. We therefore investigated the pharmacokinetics of guanosine following administration of the ACF/guanosine mixture in rats. Rats were given guanosine (1 or 5 mg/kg) or ACF/guanosine (2 or 10 mg/kg) by i.v. bolus; or guanosine (3 or 15 mg/kg) or ACF/guanosine (6 or 30 mg/kg) by i.m. injection. We found that guanosine was rapidly cleared from the blood and transferred to tissues after i.m. administration of ACF/guanosine. The mean plasma half-lives ($t_{1/2}$) at the $\alpha$ and $\beta$ phases were 0.091 and 6.86 h, or 0.092 and 7.51 h at a dose of 1 or 5 mg/kg guanosine, respectively. ACF had no effect on the plasma disappearance of guanosine following either i.v. bolus or i.m. administration of the combination mixture. Moreover, the ACF combination with guanosine did not significantly alter the values of MRT, $V_{dss}$. and $CL_t$ of guanosine. Guanosine exhibited linear pharmacokinetics over the dose range from 1 to 5 mg/kg for i.v. doses and 3 to 15 mg/kg for i.m. doses. The bioavailability of guanosine after i.m. administration was 84% for 3 mg/kg dose and 88% for 15 mg/kg dose. ACF had no effects on biliary and urinary excretion of guanosine after i.m. administration. The cumulative amount of guanosine in urine after i.m. administration was about 5-fold larger than that in bile, indicating that guanosine is mostly excreted into the urine. Guanosine was widely distributed in all tissues examined in this study, but was most highly concentrated in the kidney after i.m. administration, followed by slow excretion to bile or urine. ACF had no effect on the tissue distribution of guanosine following i.m. administration. These characterizations of the pharmacokinetics of guanosine after administration of the ACF/guanosine combination will be useful in providing preclinical and clinical bases for the potential application of this combination to the treatment of cancer.

#Guanosine #Acriflavine #Pharmacokinetics #Excretion #Distribution

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Choi, Kyu-Seok