Derivatives of benzo(c)fluorene. XVI. Absorption, distribution and elimination of 3H-benflurone, 5-(2-N,N-dimethylamino)ethoxy)-7-oxo-7H-benzo(c)fluorene hydrochloride in rats after oral and intravenous administration.

3H-benfluorone administered orally to rats, persists for a long time in the stomach; it is absorbed only partly and eliminated mostly through the feces (about 80% within 7 days). The maximum levels in the blood and the organs were determined in the 1st and 9th hour after application. Benflurone penetrates through the placentary barrier. Within one week 13% of the administered radioactivity was eliminated through the urine and 8% through the bile within 12 h. It has been demonstrated that benflurone was excreted through the milk, as well. After being administered intravenously, benflurone moves quickly from the blood into the tissues. The high levels were recorded in the heart, the lungs, the kidneys, the brain and the liver. After intravenous application about 70% of the administered radioactivity was eliminated within one week through the feces and about 24% through the urine, almost 54% through the bile within 12 h.

Biochemistry of drugs. XXIV. Substances with antineoplastic effect. LXII. Pharmacokinetics of gamma,gamma-bis-4-ethylphenyl-alpha,beta-dibromoisocrotonic acid-3H (Edikron-3H) in experimental animals.

After oral administration of Edikron-3H to mice with mammary gland adenocarcinoma HK, within 24 h after ingestion almost 50% of administered radioactivity was excreted (16% in urine, 33% in faeces), and within 4 day it was almost 80% (27% in urine, 50% in faeces). Like in mice, also in dogs the faecal excretion preponderated. In mice, the levels in most tissues and blood culminated at hour 6 after administration of the substance. Relatively high levels were found in the liver, the levels in other tissues and blood being substantially lower in comparison. The levels in the tumor were initially low, later on they rose, and culminated at hour 24. Besides, it was found that the transfer of radioactivity by milk into the sucklings' bodies was relatively low, and radioactivity penetration into fetuses was negligible. In urine, unchanged parent substance was present in very slight amounts only.

Biochemistry of drugs. XXV. Substances with antineoplastic effect. LXIII. Pharmacokinetics of delta-/2-amino-6-hydroxy-3,4-dihydro-4-oxo-5--pyrimidinyl/valeric acid-14C (Damvar-14C) in experimental animals.

In experiments on H mice and Wistar rats it was found that radioactivity was excreted after subcutaneous injection of Damvar-14C preponderantly in urine, and after oral administration, in faeces. After subcutaneous injection the urinary excretion set on very fast. After subcutaneous injection of Damvar-14C to H mice with Crocker's ascitic sarcoma S 180, peak radioactivity values were found in the majority of organs, blood, and ascitic fluid at hour 1 after injection; in the kidneys the peak value appeared as late as at hour 6. The renal levels were conspicuously higher than the other ones. Relatively high radioactivity levels were found in the ascitic fluid, skin, and blood. After oral administration the radioactivity levels in all organs, blood, and ascitic fluid culminated at hour 3 after ingestion. The highest levels after oral administration were likewise found in the kidneys and ascitic fluid. With the exception of the kidneys, blood, and skin, the peak values of specific radioactivity in organs were equally high or even higher after oral than after subcutaneous administration of the labeled substance. Furthermore, it was found that after administration of Damvar-14C to rat mothers the transfer of radioactivity into the milk and then into the sucklings was very slight, and so was the penetration of radioactivity into fetuses.

Biochemistry of drugs XXIII. Substance with antineoplastic acitivity LX. Pharmacokinetics of cis-beta-4-pentoxybenzoyl-beta-bromoacrylic acid (cis: Br, H)-3H (Penberol-3H).

After oral administration of Penberol-3H to mice with mammary gland adenocarcinoma HK, within 4 days 50% of the administered radioactivity was excreted in the urine, and 36% in the faeces. In dogs the excretion rates were slower. It was found that after oral administration of Penberol-3H to rats, radioactivity was excreted in the bile. After oral administration of Penberol-3H to mice with mammary gland adenocarcinoma, high specific radioactivities (per gram of tissue) were found in the liver, kidneys, lungs, and ovaries. Besides, it was found that after oral administration of Penberol-3H to nursing female rats the radioactivity was little eliminated in the milk, and in pregnant females its penetration into the fetuses was negligible.