The Distribution of 14C–Chloramphenicol in the Japanese Quail (Coturnix coturnix japonica)

Abstract: The distribution of ¹⁴C–labelled chloramphenicol after oral and intravenous administration to egg laying Japanese quail was studied by whole–body autoradiography. In the liver, kidneys, gizzard, intestinal contents (bile) and oviduct, the ¹⁴C–concentration was higher than that of the blood short time after injection and remained higher than the blood up to 4 days. From 4 hrs, the concentration of ¹⁴C in the egg yolks was higher than that of the blood and from 24 hrs the radioactivity in the albumen of the eggs in the oviduct was also higher than that of the blood. The peak concentration in the egg yolk was found in the second egg laid 2–4 days after administration of ¹⁴C–chloramphenicol. In the albumen the maximum concentration was found in the first laid egg 24–48 hrs after administration. In the egg yolks, about 30% of the radioactivity represented unchanged chloramphenicol up to 5 days after administration. It was also shown that about 5% of the injected ¹⁴C–chloramphenicol was exhaled as ¹⁴CO₂ during the first 12 hrs and about 37% of the dose was excreted in the combined faeces and urine during the same period of time     

The Distribution and Fate of 14C-Chloramphenicol in the New-born Pig

Abstract: The distribution of ¹⁴C-chloramphenicol has been studied in new-born pigs with the aid of whole-body autoradiography. In the lung, liver, adrenal cortex, kidney, myocardium, pancreas, thyroid, spleen and skeletal muscle the amounts of radioactivity were higher than that of the blood short time after injection and remained higher than the blood up to 8 hrs. After 4 and 8 hrs the brain concentration of ¹⁴C was also higher than that of the blood. In the bone marrow, however, the concentration did not reach that of the blood during the whole experiment. In the organs more than 90% of the radioactivity was represented by chloramphenicol; the excretory organs, thyroids, and adrenals being exceptions.     

Elimination and distribution of 2,2',4,5'-tetrachlorobiphenyl in laying hens

Laying hens were given a single oral dose of 2,2',4,5'-tetrachloro[14C]biphenyl ([14C]TCB). Within 11 days of administration, 54.8% of the original dose was excreted in the faeces. Examination of eggs laid within this period showed that 11.7% of the original dose was present in the yolks. The biological half-life of [14C]TCB in hens was 7 days. In hens killed on day 7, radioactivity could be detected in all the main tissues and organs. In both faeces and yolk, about 60% of the radioactivity could be attributed to metabolites.     

3H-莪术醇在正常大鼠及肿瘤小鼠体内的代谢研究

³H-莪术醇自大鼠胃肠道吸收迅速且完全。灌胃后5分钟血中即有放射性,15分钟达高峰,1小时仍保持较高浓度,放射性自血中消失的生物半衰期为11.5小时(t_(1/2)β)。静脉注射后血中放射性的消失分快、慢两相,生物半衰期分别为33分钟(t_(1/2)α)及12.5小时(t_(1/2)β)。放射性在正常大鼠体内分布情况与肿瘤小鼠者相似。肝及肾组织含量约为其它组织的2～2.5倍。肿瘤组织中的分布与其它组织无明显差别;组织中放射性的消失与血浆中者略呈平行关系。放射性与脂肪组织似有较强的亲和力,给药后4小时仍维持较高水平。放射性主要自尿排泄,口服或静脉注射后24小时分别自大鼠尿排出剂量的45.38%及51.91%。胆汁为另一排泄途径,大鼠口服或静脉注射后24小时,分别自胆汁排出36.47%及56.43%,而口服或静脉注射后72小时仅从粪回收6.77%及14.35%,可见,自胆汁排出的放射性大部分均又被重吸收入血。     

葛根有效成分的代谢研究——Ⅱ.14C-黄豆甙元在大鼠体内的吸收、分布和消除

本文采用纸片液体闪烁计数法研究了¹⁴C-黄豆甙元在大鼠体内的吸收、分布和消除。大鼠口服¹⁴C-黄豆甙元30分钟,血液即可测出放射性,6～8小时达高峰,以后缓慢下降。口服给药吸收不完全,由实验推论约有64.6%放射性可被吸收。静脉注射后,血放射性消失曲线分为快、慢两个时相,其生物半衰期分别为13分钟和42分钟。放射性在肾、肝含量最高,血浆、肺、心次之,肌肉、脾、睾丸、脑较低。静脉注射后,¹⁴C主要自尿排出(24小时可排出剂量的71.2%),自粪排出17.4%。口服后24小时可自尿排出34.3%,自粪排出33.1%。胆汁也是一条重要排泄途径,静脉注射后24小时可自胆汁排出剂量的47.4%;口服后相应时间内排出39.1%。本文所得结果与前文应用化学方法所得结果进行比较,表明自消化道、尿、胆汁所回收的放射性主要是黄豆甙元的代谢产物,说明该药在体内的代谢很旺盛。     

Distribution, metabolism and excretion of 14C-MT-141 in rats. II. Distribution and excretion after multiple intravenous administration in male rats and after single intravenous administration in female rats

The distribution and tissue accumulation of the radioactivity were studied in male rats after the multiple intravenous administration of 14C-MT-141. The distribution and the placental transfer were also studied using pregnant rats or lactating rats after the single intravenous administration of 14C-MT-141. The radioactive concentration in the fetus was low and the radioactivity was distributed almost uniformly through the fetus body. The peak time of the milk level was 2 hours after the administration and the radioactivity in milk decreased gradually thereafter. The milk levels decreased more slowly than the blood levels did. The blood level after the last dose administered daily for 7 days tended to decrease more slowly, when compared with the single administration. However the blood concentration at 48 hours after the last administration was less than 3 times as high as that after the single administration.     

Studies on absorption, distribution and excretion of 14C labeled (+-)-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1-(2,4-difluorophenyl)-1,4- dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid p-toluene-sulfonate hydrate (14C-T-3262) in rats and mice

Absorption, distribution and excretion of T-3262 were studied in rats and mice after oral administration of 14C-T-3262. The obtained results are summarized as follows. 1. 14C-T-3262 was absorbed from the upper small intestine such as duodenum in rats. 2. Serum levels of radioactivity in rats reached the highest concentration at 1 hour after an oral administration, then gradually diminished. 3. Urinary excretion was 35% and 42% of the dosed radioactivity in rats and mice, respectively, and fecal excretion was about 65% and 56% of the dosed radioactivity in rats and mice, respectively. 4. Biliary excretion in rats was about 27% of the dosed radioactivity after an oral administration of 14C-T-3262, and a half amount of excreted radioactivity was reabsorbed from the intestine. 5. Radioactivity was distributed the most into the kidney and the liver among all organs other the stomach and the intestine. Radioactivity was widely distributed into other organs such as spleen, adrenal, pancreas, lung, heart and thymus. But the distribution of radioactivity into the brain was little. 6. The distribution of 14C-T-3262 was also studied with whole body autoradiography in normal male mice and pregnant mice. The radioactivity was distributed widely to whole tissues except brain, spinal cord and eye ball. In pregnant mice, radioactivity levels in the fetuses were the same as the blood level of the mother mice. 7. The binding rate of 14C-T-3262 to rats and mice serum proteins was 63-66%. 8. Urinary and fecal excretion patterns of radioactivity in mice after multiple oral administration of 14C-T-3262 for 10 days were similar to those after a single administration. This result suggests that T-3262 did not accumulate in body. 9. After oral administration of 14C-T-3262 to nursing rats, the secreted radioactivity level in the milk was higher than the blood level.     

Studies on the metabolic fate of 14C-rokitamycin. II. Accumulation of radioactivity in rats after consecutive oral administration

After a consecutive oral administration of 200 mg/kg/day of 14C-rokitamycin (TMS-19-Q) daily for 28 days to male rats, the accumulation of radioactivity in tissues and its disappearance after the cessation of the administration was studied. Blood concentrations at peak times and 24 hours after each administration were determined daily. Both values increased gradually until the 14th day and thereafter remained roughly constant. The extent of elimination of radioactivity from the blood was practically not affected by the consecutive administration. Affinities of radioactivity to the liver, kidney, spleen, adrenal, pituitary gland, preputial gland, thyroid, intraorbital lacrimal gland and bone marrow were comparatively higher than those to other tissues. Tissue concentrations in the above mentioned tissues at the 1st day after the completion of consecutive administrations for 14 and 28 days were 2.6-6.1 and 3.2-6.8 times higher, respectively, than those at the 1st day after a single administration. The elimination of radioactivity from the tissue after the consecutive administration for 28 days was slightly slower than that after a single administration. In the consecutive daily administration for 28 days, the metabolic fate of radioactivity reached a steady state after 14 days of consecutive daily administration. Hence, the accumulation of the radioactivity did not particularly occurred. During the consecutive administration, recoveries of radioactivity in the urine and feces were almost at a constant rates, with 8.0 and 93.8% of the total radioactivity given excreted in the urine and feces, respectively, within 10 days after the last administration.     

Pharmacokinetics and disposition of a new antitumor antibiotic (2'R)-4'-O-tetrahydropyranyladriamycin in rats. Distribution and excretion after multiple administration

The accumulation of (2'R)-4'-O-tetrahydropyranyladriamycin (THP) was studied in rats received intravenous administration of 14C-THP at a dose of 0.5 mg/kg/day for 14 consecutive days by determining blood and tissue levels and the excretion of the radioactivity. The radioactivity levels in plasma and blood cells after the multiple administration were higher than those after single administration. The half-life of the radioactivity after the multiple administration was longer in the blood cells but not in the plasma than the half-life after a single administration. Tissue levels of the radioactivity after the multiple injection were 2 to 4 times as high as the levels after a single injection except for the brain and testes in which a large accumulation of the radioactivity was observed. However, little accumulation of unlabeled THP was found in most tissues when determined by HPLC. The accumulation of radioactivity in tissues, therefore, was due to metabolites of THP. The disposition of 14C-THP was also examined in rats which had previously received unlabeled THP (0.5 mg/kg/day) for 13 days. The pretreatment did not affect the disposition of 14C-THP seriously, although the pretreatment raised tissue levels slightly and a rebound of plasma level of 14C-THP, and lowered the fecal excretion ratio. No induction of hepatic drug metabolizing enzymes was observed in rats after repeated administrations of THP for consecutive 14 days.     

Study on the metabolic fate of catena-(S)-[mu-[N alpha-(3- aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc]. 2nd communication: absorption, distribution, metabolism and excretion after repeated administration to rats.

After repeated administration of 14C-Z-103 (catena-(S)-[mu-[N alpha-(3- aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7) to rats for 21 days, the accumulation of radioactivity in the blood and tissues was proportional to the number of doses given. Following treatment of the terminal blood, plasma, liver and kidney samples with trichloroacetic acid (TCA) or protease, the radioactivity in these tissues was demonstrated to be TCA-insoluble and solubilized by the protease treatment. Thus, the accumulation of radioactivity after repeated administration of 14C-Z-103 was considered to be due to the utilization of the metabolites of L-carnosine, the constituent of Z-103, into a protein. The cumulative ratios of radioactivity excreted into the urine, feces and expired air and the radioactivity remaining in the carcass after repeated administration of 14C-Z-103 for 21 days were similar to those values obtained after a single administration, suggesting that repeated administration did not influence the excretion profile of Z-103. During the period of repeated administration of non-radioactive Z-103 to rats for 21 days, the fecal content of zinc was higher than that in nontreated rats, whereas it returned to the control level at 48 h after the final administration. There was no significant difference in the urinary concentration of zinc between treated and non-treated animals during the period of repeated administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Toxicity and distribution of 2-methyl-4-chlorophenoxyacetic acid (MCPA) in developing chick embryos

The toxicity of the herbicide Erbitox E30, a commercial formulation of 2-methyl-4-chlorophenoxyacetic acid (MCPA) containing 28% MCPA as sodium-potassium salt and 72% of unknown ingredients, was tested on chick embryos. Sterile aqueous solutions of MCPA were injected into the air chamber at doses of 0, 1.5, 3.0, 6.0, 9.0, or 10.5 mg/egg on day 0 or on day 4 of incubation. The mortality rate for the embryos treated on day 0 of incubation was high in the first 5 days, low from 5-12 days and again increased by 15 days. The 15-day LD50 was 4.4 mg/egg (95% C.I. 3.7-5.3 mg/egg). HPLC analysis of albumen and yolk showed that concentrations of MCPA in the albumen were detectable at 5 min, highest at 7 days and markedly diminished by 14 days of incubation; a significantly lower concentration of MCPA was found in the yolk throughout the incubation period, except at 14 days when the yolk concentration was 4 times higher than the albumen concentration. At 15 days of incubation, MCPA was evenly distributed in the tissues of the embryo. MCPA was more toxic to 4-day embryos; concentrations above 6.0 mg/egg were lethal to all embryos within the first week of incubation. The 15-day LD50 for treatment on day 4 of incubation was 2.8 mg/egg (95% C.I. 2.5-3.2 mg/egg). The liver was affected by treatment with MCPA, being green in treated embryos. However, histological examination revealed few changes in the liver parenchyma.     

Tissue distribution and pharmacokinetics of 3-t-[methyl-14C] butyl-4-hydroxyanisole in rats

Tissue distribution and pharmacokinetics of 3-t-[methyl-14C]butyl-4-hydroxyanisole was studied in male rats. 3-t-[methyl-14C]butyl-4-hydroxyanisole was administered by gavage at a single dose of 1.5 mmol/kg. Urine, feces, blood, and 20 major tissues were collected at 0.5, 1, 3, 6, 12, 16, 17, 18, 24, 48, 72, 168, and 240 hr after dosing and were analyzed for radioactivity. Almost all radioactivity was eliminated from rats in 48 hrs. Forty one per cent of the administered dose was recovered in urine, while feces accounted for 53%. At early time points radioactivity was mainly found in gastrointestinal tissues with concentrations remaining high up to 16-18 hr after administration indicating a slow absorption and elimination of the compound. The maximum concentration of radiolabel in kidney, liver, bladder, spleen, heart, pancreas, and brain was reached at 6 hr and remained up to 24 hr. The concentration of radioactivity in liver and kidney was approximately 10-fold higher than other tissues at the peak time of 16-18 hrs. Calculated absorption and elimination rate constants demonstrated slow uptake and clearance of label by many tissues. Covalent binding in eight representative tissues at 10 time points was also studied. Results indicate that binding increases slowly and exponentially with time reaching maximum levels at 12-24 hr in most of the tissues followed by a slow decline with time.     

The Distribution of 14C-Ethoxyquin in Rat

Abstract Adult male rats were given the antioxidant ¹⁴C-ethoxyquin by oral intubation and were sacrificed at various time intervals from 0.5 hr to 6 days following administration of the drug. The distribution pattern was studied by whole-body autoradiography and liquid scintillation counting. The isotopelabelled antioxidant was distributed throughout most tissues and the blood at 0.5 hr after administration. The highest radioactivity throughout the experimental period was observed in the liver, the kidney, the gastrointestinal tract and the adipose tissue. No activity was observed in the brain and the central nervous system. Of the dose ingested 2.2 and 0.2% were found in the liver at 0.5 hr and 6 days respectively following dosing. The hepatic peak in radioactivity was measured at 8 hrs and after 6 days 7.5% of this level was still present in the liver. Six days after administration residues of ethoxyquin and metabolites were also present in the kidney cortex, the intestines, the lung, various adipose tissue and blood.     

The distribution of 14C-ethoxyquin in rat.

Adult male rats were given the antioxidant 14C-ethoxyquin by oral intubation and were sacrificed at various time intervals from 0.5 hr to 6 days following administration of the drug. The distribution pattern was studied by whole-body autoradiography and liquid scintillation counting. The isotopelabelled antioxidant was distributed throoughout most tissues and the blood at 0.5 hr after administration. The highest radioactivity throughout the experimental period was observed in the liver, the kidney, the gastrointestinal tract and the adipose tissue. No activity was observed in the brain and the central nervous system. Of the dose ingested 2.2 and 0.2% were found in the liver at 0.5 hr and 6 days respectively following dosing. The hepatic peak in radioactivity was measured at 8 hrs and after 6 days 7.5% of this level was still present in the liver. Six days after administration residues of ethoxyquin and metabolites were also present in the kidney cortex, the intestines, the lung, various adipose tissue and blood.     

Distribution of 14C-ochratoxin A in the mouse monitored by whole-body autoradiography

The tissue distribution of 14C-labeled ochratoxin A was studied in mouse using whole-body autoradiography. The distribution was followed for 18 days after one single intravenous injection of 5 microCi/animal, corresponding to 160-230 ng toxin/g body weight. Very long persistence of 14C-ochratoxin A in the circulation was noticed and the toxin was detected in the blood even after 18 days when the experiment was finished. The radioactivity in the kidney was unequally distributed with a slightly higher concentration in the inner cortical and medullary parts. This was seen from 24 hrs and on after injection. Very high concentrations of radioactivity were found in the bile of treated animals. The radioactivity extracted from several sections was chemically characterized with thin-layer chromatography and was found to represent 14C-ochratoxin A.     

Nasal drug delivery system of a quaternary ammonium compound: clofilium tosylate

The blood levels of the [14C]clofilium ion in rats after various routes of administration of clofilium tosylate were compared. The results indicate that the blood levels after nasal administration were not statistically different from levels after intravenous administration (p greater than 0.05). Administration by the oral route resulted in considerably lower blood levels. Nasal administration of clofilium tosylate appeared to be superior to oral administration. Histological examinations of nasal mucosa were conducted. At the lower concentration, mild necrosis was observed, and large areas of mucosa were unaffected. However, necrosis of large areas of mucosa occurred after exposure to the higher concentration. Levels of radioactivity in heart, liver, lung, and kidney tissue, as a function of time, were also studied. Unlike the blood levels after nasal administration, the levels of radioactivity were persistent in heart tissue. The data suggest that the [14C]clofilium ion and/or metabolite concentrate in the heart and that blood levels of radioactivity may not be an accurate index of cardiac levels or biological response.     

Tissue Distribution of 14C-Rifampicin I. Whole Body Autoradiography of Albino Mice

Abstract: Whole body autoradiography of albino mice 5, 20, 60 min., 4, 24 hrs and 4 days after a single intravenous injection of ¹⁴C-rifampicin showed that rifampicin and/or its metabolites were rapidly distributed into most organs. As early as 5 min. after the injection, the lung, myocardium, brown fat, salivary glands, gastrointestinal mucosa, pancreas, kidney and liver showed higher uptake than the blood. A blood-brain barrier was apparent. A very high uptake was initially observed in the liver. Most of the radioactivity had disappeared after 24 hrs, although slight activity was still seen in the liver and thyroid after 4 days. No other specific retention of toxicological interest was observed.     

Studies on absorption, distribution and excretion of 14C labeled pivaloyloxymethyl (+)-(6R,7R)- 7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]- 3-[(5-methyl-2H-tetrazol-2-yl)methyl]-8-oxo-5-thia- 1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate (14C-T-2588) in rats and mice

Absorption, distribution and excretion of T-2588 were studied in rats and mice using (aminothiazole-2-14C) T-2588 and (pivaloyloxymethyl-14C) T-2588. Results are summarized below. The binding rate of 14C-T-2525, an activated form of 14C-T-2588 in vivo, to serum protein was 90 approximately 100% in rats and mice after an oral administration of (aminothiazole-2-14C) T-2588. Blood levels of radioactivity reached to the highest concentration at 1 hour after an oral administration of (aminothiazole-2-14C) T-2588 to rats, and then gradually diminished. After an oral administration of (aminothiazole-2-14C) T-2588 to rats and mice, the highest radioactivity distribution was found in kidney among all the organs except stomach, intestine and bladder. Radioactivity was widely distributed into other organs such as adrenal, lung, liver, heart and pancreas. But little radioactivity was found in the brain. In new born rats, tissue levels of radioactivity were lower and diminished slower than those of adult rats. After an oral administration of (aminothiazole-2-14C) T-2588 to rats and mice, urinary excretion of radioactivity was about 26% and 35% of the dosed radioactivity in rats and mice, respectively, and fecal excretion was about 76% and 63% of the dosed radioactivity in rats and mice, respectively. Urinary and fecal excretion patterns of radioactivity after multiple oral administration of (aminothiazole-2-14C) T-2588 for 7 days to mice were similar to those after a single administration. This result suggests that T-2588 did not accumulate in the body. After an oral administration of (pivaloyloxymethyl-14C) T-2588 to rats and mice, urinary excretion was both about 8% of the dosed radioactivity, and fecal excretion was both about 6%. Then excretion of 14CO2 into respiratory air was about 55% and 66% of the dosed radioactivity in rats and mice, respectively. Biliary excretion was about 6.5% of the dosed radioactivity after an oral administration of (aminothiazole-2-14C) T-2588 to rats. Small amount of radioactivity was secreted to the milk after intravenous administration of (aminothiazole-2-14C) T-2525 to nursing rats. After an administration of (aminothiazole-2-14C) T-2588 to pregnant mice, radioactivity hardly transferred into the fetus.     

The absorption, tissue distribution and excretion of di-n-octyltin dichloride in rats

In this study the absorption, tissue distribution and excretion of 14C-labeled di-n-octyltin dichloride ([14C]DOTC) in rats were investigated after oral and intravenous (i.v.) administration. Although after i.v. administration with 1.2 mg [14C]DOTC/kg body weight the tissue radioactivity was about 3-4 times higher than after oral administration with 6.3 mg [14C]DOTC/kg body weight, the relative tissue accumulation was found to be the same after the oral and i.v. dosage. The highest amount of radioactivity was found in liver and kidney, and to a lesser degree in adrenal, pituitary and thyroid glands. The lowest activity was recovered from blood and brain. No selective accumulation was observed in thymus, although it has been reported that thymus atrophy is the most sensitive parameter of DOTC toxicity in rats. For all tissues a time dependent decrease in radioactivity was found, except for kidney. The excretion of radioactivity in feces and urine was determined after a single i.v. or oral dose of 1.2 and 2 mg [14C]DOTC, respectively. After i.v. administration most of the radioactivity was excreted in the feces which was characterized by a biphasic excretion pattern. In orally treated rats more than 80% of the radioactivity was already excreted in the feces during the first day after administration. This indicated that only a small part of the DOTC was absorbed, which was calculated to be approximately 20% of the dose. Similar half-life values of 8.3 and 8.9 days were obtained from the fecal excretion of radioactivity after the i.v. and oral administration, respectively. The urinary excretion of radioactivity appeared to be independent of the body burden, since the daily amount of radioactivity excreted in urine was nearly the same independent of the route of administration as well as the time after administration.     

Tissue distribution of [14C]DDT in the lobster after administration via intravascular or oral routes or after exposure from ambient sea water

A pharmacokinetic approach to studying the fate and distribution of [¹⁴C]DDT was employed using the lobster, a species of obvious economic importance. The radioactive pesticide was administered by 3 different routes; intravascular, oral and by exposure from the ambient water. After intravascular administration there was very rapid removal of [¹⁴C]DDT from the plasma accompanied by a strikingly persistent increase in the amount of radioactivity in the hepatopancreas. Most (>90%) of the radioactivity in this organ was shown by TLC to be the parent pesticide. Seven days after injection of [¹⁴C]DDT approximately 90% of the administered radioactivity was found in the hepatopancreas and the concentrations in this organ decreased with a $\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ of 46 days. One month after treatment with 0.1 mg/kg of [¹⁴C]DDT, the only other organs which contained more than 1% of the administered dose were egg masses and muscle. When the pesticide was administered to the lobster from ambient water or from food, the hepatopancreatic compartment again dominated, with more than 90% of the absorbed dose occurring in this organ 7 days after treatment. Studies conducted of residue levels in untreated lobsters indicated that the egg masses contained the largest concentration of total DDT metabolites (1 ppm). The hepatopancreas contained about 0.4 ppm while the carcass (muscle) contained about 0.1 ppm. These distribution studies suggest that while the lobster may protect itself from DDT toxicity by sequestering the pesticide in the hepatopancreas and in egg masses, bioconcentration in these tissue could be hazardous to species consuming these parts of the lobster.