Detail of "86189-66-4"

Reference

Activity and distribution of i

Activity and distribution of i.v. and oral 4-demethoxydaunorubicin in murine experimental tumors.Some chemicals with cas registry numbers like 86189-66-4 and 58957-92-9 are also used. Broggini, M.; Italia, C.; Colombo, T.; Marmonti, L.; Donelli, M. G. (Ist. Ric. Farmacol. "Mario Negri", Milan 20157, Italy). Cancer Treat. Rep., 68(5), 739-47 (English) 1984. CODEN: CTRRDO. ISSN: 0361-5960. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The antitumor activity of 4-demethoxydaunorubicin (4DDM)(I) [58957-92-9] compared to its parent compd. daunorubicin (DM) was investigated in C57BL/6 mice bearing a T-cell lymphoma (EL-4). 4DDM was moderately effective against Lewis lung carcinoma and M5076/73A ovarian reticulosarcoma tumor systems. Against the EL-4 tumor, after either i.v. or oral treatment, 4DDM had a good therapeutic effect (survival time in treated mice was almost double that in untreated mice) which was comparable to that of i.v. doxorubicin. Serum and tissue distribution of 4DDM and its reduced metabolite 4-demethoxydaunorubicinol [86189-66-4], given either i.v. or orally at therapeutic doses to EL-4-bearing mice, was then compared with i.v. DM. DM seemed to be cleared faster and to a greater extent by metab. than 4DDM, with half-lives after i.v. treatment of 23 h for 4DDM vs. 4.6 h for DM. The amt. of reduced metabolite in serum amounted to >100% of the concn. of the native compd. for DM and <20% for 4DDM. After both the i.v. and oral administration, 4DDM appeared to be concd. and retained in tissues to a proportionally higher extent than DM, with drug exposure being at least twice as high with correspondingly longer half-lives in almost all tissues investigated, including the tumor. Moreover, this demethoxy analog appeared to be somewhat more selective than DM, since the relative capacity of the tumor tissue to accumulate this compd. seemed higher than that of other organs (eg, heart and spleen) reported to be targets of toxicity. Oral administration gave more favorable distribution, resulting in the highest tumor to heart and spleen concn. ratio; this suggests a superiority of this route of administration. .

Pharmacokinetics of idarubicin in the isolated perfused rat lung: effect of cinchonine and rutin

Pharmacokinetics of idarubicin in the isolated perfused rat lung: effect of cinchonine and rutin. Kuhlmann, Olaf; Hofmann, Hans-Stefan; Mueller, Sylvana P.; Weiss, Michael (Section of Pharmacokinetics, Martin-Luther University, Halle, Germany). Anti-Cancer Drugs, 14(6), 411-416 (English) 2003 Lippincott Williams & Wilkins. CODEN: ANTDEV. ISSN: 0959-4973. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) This study was designed to examine the effect of rutin and cinchonine on the uptake and metab. of idarubicin (IDA) in the isolated perfused rat lung. IDA (2 mg) was infused for 2 min into the truncus pulmonalis in the presence of P-glycoprotein (P-gp) modulators cinchonine (1 mM) or rutin (6 mM). (Rutin is also known as an aldo-keto reductase inhibitor.). Venous outflow samples were collected up to 60 min, and the concn. of IDA and its primary metabolite idarubicinol (IDOL) were measured by high-performance liq. chromatog. with fluorescence detection. Thereafter, the tissue concns. of IDA and IDOL were detd. in the lung (n = 5 in each group). The estd. mean transit times for IDA in the treatment groups (MTTcinchonine = 21.8±3.5 min; MTTrutin = 20.1±5. 118-10-5 and 86189-66-4 are cas registry numbers of chemicals which are used as reagents here.0 min) were significantly higher than in the control group (11.6±2.1 min). Both cinchonine and rutin significantly enhanced the lung tissue concns. of IDA (1.7- and 2.4-fold), as well as of IDOL (2.1- and 2.4-fold). Cinchonine and rutin also increased the outflow recovery of IDOL 2.6- and 2.7-fold, resp. The results suggest that uptake kinetics of IDA into the rat lung is partly controlled by a P-gp efflux pump and its inhibition enhances the accumulation of IDA. .