The distribution of 14C-chloramphenicol in the Japanese quail (Coturnix coturnix japonica)

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.     

The Metabolism of Biphenyl. I. Metabolic Disposition of 14C–Biphenyl in the Rat

Abstract The metabolic disposition of ¹⁴C–biphenyl in the rat was studied by liquid scintillation counting. The rats were given an oral dose of ¹⁴C–biphenyl (100 mg/kg, 0.7–1.0 μci) and the total excretion of radioactivity after 96 hrs was 92.2 % of the dose. Urinary excretion accounted for 84.8 % and faecal excretion for 7.3% of the dose. Most of this radioactivity, 75.8 % and 5.8% respectively, was excreted within 24 hrs. Only trace amounts of ¹⁴CO₂ were detected in the expired air and 0.6% of the dose was found to be still present in the rats 96 hrs after biphenyl administration. Extraction and fractionation of the 24 hrs urine samples showed that the largest fraction (nearly 30% of the dose) consisted of conjugated phenolic metabolites. Acidic metabolites accounted for a quarter of the dose and the low levels of expired ¹⁴CO₂ indicated that these were not products resulting from extensive degradation and decarboxylation.     

Metabolism and pharmacokinetics of a single oral dose of O-4-bromo-2,5-dichlorophenyl O-methyl phenylphosphonothioate (Leptophos) in hens

The metabolism and pharmacokinetics of a subneurotoxic dose of leptophos were determined in laying hens following a single oral dose of 50 mg/kg (0.9 μCi/hen) of [phenyl¹⁴C]leptophos (O-4-bromo-2,5-dichlorophenyl O-methyl [¹⁴C]phenylphosphonothioate). This study adds confirmatory evidence to the hypothesis that species selectivity for delayed neurotoxicity is related to interspecies differences in pharmacokinetics and metabolism. Oral leptophos was metabolized and excreted slowly in hens. The major portion of the radioactivity (86.5%) was excreted during the 20-day experiment. Significant amounts of the dose were deposited in egg albumen and yolk—3.4 and 2.5%, respectively. Only 1.3% was excreted in expired CO₂. Radioactivity in tissues reached a peak of 14.6% of the dose 12 hr after administration; radioactivity decreased to 6.2% after 20 days (42.6% of peak value). The highest ¹⁴C concentration was present in the bile, followed by the gall bladder, kidney, adipose tissue, and liver. Brain, spinal cord, and sciatic nerve, which are affected by the neurotoxicity of leptophos, had smaller but constant concentrations throughout the experiment. Following the oral administration of [¹⁴C]leptophos the change in the ¹⁴C body burden with time was biexponential. The physiological disposition of leptophos may therefore be defined in terms of a two-compartment open-system model. Radioactivity was excreted at a slow rate, β value of 0.05 day^?1, corresponding to a half-life of 12.0 days. Leptophos was the only compound identified in nerve tissues, muscle, fat, and blood. Most of the radioactive substances in the excreta and liver were identified as unchanged leptophos with minor amounts of polar metabolites. The metabolic fate of leptophos can be explained on the basis of its physical properties of lipid solubility and tissue binding, and the predominant biliary secretion and gastrointestinal excretion of the compound.     

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 and Elimination of 2–MethyI–4–Chlorophenoxyacetic Acid (MCPA) in Male Rats

Abstract The distribution and elimination of 2–methyl–4–chlorophenoxyacetic acid (MCPA) in male rats were studied. 3 mg of ¹⁴C–labelled and non–labelled MCPA in 50 % ethanol was injected into the stomach of male rats and urine, faeces and internal organs or tissues were analyzed for radioactivity. During the first 24 hrs 92.26 ± 5.36 % of the radioactivity was excreted in the urine and 6.76 ± 3.56 % in the faeces. Recovery in the urine and faeces after five days was 102.78 ± 1.10 % of the dose administered, indicating that practically all MCPA is eliminated in the urine and faeces. The maximum concentrations of MCPA in the tissues occurred between 2 to 8 hrs after administration. Thereafter the concentrations declined rapidly. The highest concentrations of MCPA were observed in the blood, kidney, lung, heart, suprarenal gland, liver, thyroid gland and bone marrow. The lowest concentrations were those in the brain, adipose tissue, testis and muscle.     

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。     

Pharmacokinetics and metabolism of a topically applied dose of O-4-bromo-2,5-dichlorophenyl O-methyl phenylphosphonothioate in hens.

Investigations into the pharmacokinetics and metabolism of a topically applied 50 mg/kg dose of ¹⁴C-labeled leptophos (O-4-bromo-2,5-dichlorophenyl O-methyl [¹⁴C]phenylphosphonothioate) on the comb of hens are reported. A total of 35.4% of the applied dose was absorbed through the skin during the 20-day experiment. Combined urinary-fecal excreta accounted for most of the radioactivity (24.3% of the applied dose). Significant amounts of the dose were deposited in egg albumen and yolk: 2.5 and 2.0%, respectively. Only 1.3% was excreted in expired CO₂. Radioactivity in tissues reached a peak of 17.1% of the dose 12 hr after administration; radioactivity decreased to 5.0% after 20 days (29.4% of peak value). Highest ¹⁴C content was present in the muscle, followed by the skin, adipose tissue, and the liver. Central and peripheral nerve tissues were shown throughout the experiment to contain small constant amounts of ¹⁴C. The change in the ¹⁴C in the body with time showed a biphasic pattern. The half-life for the elimination of ¹⁴C from the bird's body was 17.0 days corresponding to a rate value β of 0.04 day^?1. Most of the radioactive substances in the excreta and liver were identified as unchanged leptophos with minor amounts of polar metabolites. The fate of leptophos was rationalized on the basis of its physical properties, i.e., lipid solubility and tissue binding, and predominant biliary secretion and gastrointestinal excretion.     

Comparative Studies on the Metabolic Disposition of 8-Chloro-6-pheny1–4H-s-triazolo[4,3-a][1,4]benzo-diazepine (D-40TA) and Nitrazepam after Single and Repeated Administration in Rats

Abstract

1. Orally administered D-40TA was absorbed by rats with a maximum blood level at 30 min and a half-life of 60 min. The blood level of orally administered nitrazepam reached a plateau which persisted for 90 min and then declined with a half-life of 90 min.

2. Both D-40TA and nitrazepam crossed the blood-brain barrier of rats. The 1-oxo metabolite of D-40TA is pharmacologically active, and also readily entered the brain.

3. Orally administered D-40TA and nitrazepam were eliminated in urine and faeces over 3 days, the larger part in faeces. In both cases, about 90% of the dose of radioactivity was eliminated from the body during the first 2 days after administration.

4. After intravenous injection of either [¹⁴C]D-40TA or [¹⁴C]nitrazepam, the radioactivity was excreted in bile at the same rate, 69 and 64% of the dose being recovered from the 24 h-bile, respectively. The biliary metabolites of both benzodiazepines underwent entero-hepatic cycling.

5. After daily oral administration of [¹⁴C]D-40TA or [¹⁴C]nitrazepam, the cumulative excretion closely paralleled the dosage of radioactivity. For both drugs, excretion was complete within 3 days of discontinuing medication. During repeated administrations of the labelled drugs, no increase in concn. of blood radioactivity 1 h after dosing was observed. With [¹⁴C]D-40TA-treated rats, most of the radioactivity still in the body 24 h after administration was recovered from the gastro-intestinal contents; only small amounts were in tissues. Dosing of [¹⁴C]D-40TA for 7 days caused no increase in tissue levels of radioactivity, except in the liver, where the radioactivity increased to about twice the level noted after a single administration.     

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.     

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.     

Pharmacokinetics of a neurotoxic oral dose of leptophos in hens

A pharmacokinetic profile of [¹⁴C] leptophos was determined in laying hens following a single oral dose of 400 mg/kg (0.58 Ci). Most of the radioactivity was excreted into the urine and feces. After 15 days, the total radioactivity recovered in the combined urinary-fecal excretion was 73.5% of the administered dose. A major part of the absorbed leptophos was concentrated in the eggs. The total ¹⁴C radioactivity in egg albumen was 7.29% of the administered dose as compared to 4.67% in egg yolk. The half-life for the disappearance of radioactivity from the birds' bodies following the administration of [¹⁴C] leptophos was 11.55 days. A correlation between the pharmacokinetics of leptophos and the susceptibility of the hen to delayed neurotoxicity is discusses.

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Zusammenfassung Die Pharmakokinetik von ¹⁴C-Leptophos wurde an Legehennen nach einmaliger oraler Gabe von 400 mg/kg (0,58 Ci) untersucht. Der Hauptanteil der Radioaktivität wurde in Urin und Faeces ausgeschieden. Nach 15 Tagen betrug die insgesamt in Urin und Faeces wiedergefundene Radioaktivität 73,5% der applizierten Dosis. Ein größerer Teil des resorbierten Leptophos wurde in den Eieren angereichert. Die gesamte ¹⁴C-Radioaktivität betrug im Eiklar 7.29% und im Eigelb 4.67% der applizierten Dosis. Die Halbwertzeit für das Verschwinden der Radioaktivität aus dem Körper der Vögel nach der Gabe von ¹⁴C-Leptophos betrug 11,55 Tage. Eine Korrelation zwischen der Pharmakokinetik von Leptophos und der Empfindlichkeit der Henne hinsichtlich verzögerter Neurotoxizität wird diskutiert.

     

Paraquat disposition in rats, guinea pigs and monkeys

LD50 doses of ¹⁴C-labeled paraquat were administered to rats, guinea pigs and monkeys by gavage, and radioactivity was determined in excreta and tissues. Rat urine was analyzed for paraquat metabolites by thin-layer chromatography. [¹⁴C]Paraquat was absorbed from the gastrointestinal tract and reached highest serum values 0.5–1 hr after administration. Disappearance of [¹⁴C]paraquat from serum was characterized by a rapid initial decline followed by a prolonged slow decline. Tissue paraquat values were higher than serum values in rats and guinea pigs. Relative to other tissues, paraquat accumulated transiently in the lung and reached peak concentration 32 hr after administration. In rats a major portion of administered paraquat was not absorbed from the gastrointestinal tract. At 32 hr after paraquat, 52% of the administered dose remained in the gastrointestinal tract and 17 and 14% of the administered dose was excreted in the feces and urine, respectively. No radioactivity was recovered in expired air or flatus. Excretion of paraquat in urine and feces was prolonged in all species. In monkeys paraquat was measured in urine and feces 21 days after administration. Chromatography of urine from [¹⁴C]paraquat-treated rats revealed no metabolites. The primary pathologic changes induced by paraquat in the lung may be related to the transient uptake of the chemical by that organ.     

Absorption,distribution and excretion of the anti‐tuberculosis drug delamanid in rats: Extensive tissue distribution suggests potential therapeutic value for extrapulmonary tuberculosis

Delamanid (OPC‐67683, Deltyba™, nitro‐dihydro‐imidazooxazoles derivative) is approved for the treatment of adult pulmonary multidrug‐resistant tuberculosis. The absorption, distribution and excretion of delamanid‐derived radioactivity were investigated after a single oral administration of ¹⁴C–delamanid at 3 mg/kg to rats. In both male and female rats, radioactivity in blood and all tissues reached peak levels by 8 or 24 h post‐dose, and thereafter decreased slowly. Radioactivity levels were 3‐ to 5‐fold higher in lung tissue at time to maximum concentration compared with plasma. In addition, radioactivity was broadly distributed in various tissues, including the central nervous system, eyeball, placenta and fetus, indicating that ¹⁴C–delamanid permeated the brain, retinal and placental blood barriers. By 168 h post‐dose, radioactivity in almost all the tissues was higher than that in the plasma. Radioactivity was also transferred into the milk of lactating rats. Approximately 6% and 92% of radioactivity was excreted in the urine and feces, respectively, indicating that the absorbed radioactivity was primarily excreted via the biliary route. No significant differences in the absorption, distribution and excretion of ¹⁴C–delamanid were observed between male and female rats. The pharmacokinetic results suggested that delamanid was broadly distributed to the lungs and various tissues for a prolonged duration of time at concentrations expected to effectively target tuberculosis bacteria. These data indicate that delamanid, in addition to its previously demonstrated efficacy in pulmonary tuberculosis, might be an effective therapeutic approach to treating extrapulmonary tuberculosis. Copyright © 2017 John Wiley & Sons, Ltd.     

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.     

Absorption,distribution, metabolism and excretion of loxoprofen after dermal application of loxoprofen gel to rats

Abstract

1. Loxoprofen (LX), is a prodrug of the pharmacologically active form, trans-alcohol metabolite (trans-OH form), which shows very potent analgesic effect. In this study, the pharmacokinetics and metabolism of [¹⁴C]LX-derived radioactivity after dermal application of [¹⁴C]LX gel (LX-G) to rats were evaluated.

2. The area under concentration-time curve (AUC_0–∞) of radioactivity in the plasma after the dermal application was 13.6% of that of the oral administration (p?<?0.05).

3. After the dermal application, the radioactivity remained in the skin and skeletal muscle at the treated site for 168?h, whereas the AUC_0–168?h of the radioactivity concentration in every tissue examined except the treated site was statistically lower than that after the oral administration (p?<?0.05).

4. The trans-OH form was observed at high levels in the treated skin site at 0.5?h. Metabolite profiles in plasma, non-treated skin site and urine after the dermal application were comparable with those after the oral administration.

5. Renal excretion was the main route of elimination after the dermal application.

6. In conclusion, compared to the oral administration, the dermal application of [¹⁴C]LX-G showed lower systemic and tissue exposure with higher exposure in the therapeutic target site. The radioactivity revealed similar metabolite profiles in both administration routes.     

Distribution and biomarkers of carbon‐14‐labeled fullerene C60 ([14C(U)]C60) in female rats and mice for up to 30 days after intravenous exposure

A comprehensive distribution study was conducted in female rats and mice exposed to a suspension of uniformly carbon‐14‐labeled C₆₀ ([¹⁴C(U)]C₆₀). Rodents were administered [¹⁴C(U)]C₆₀ (~0.9 mg kg^?1 body weight) or 5% polyvinylpyrrolidone‐saline vehicle alone via a single tail vein injection. Tissues were collected at 1 h and 1, 7, 14 and 30 days after administration. A separate group of rodents received five daily injections of suspensions of either [¹⁴C(U)]C₆₀ or vehicle with tissue collection 14 days post exposure. Radioactivity was detected in over 20 tissues at all time points. The highest concentration of radioactivity in rodents at each time point was in liver, lungs and spleen. Elimination of [¹⁴C(U)]C₆₀ was < 2% in urine and feces at any 24 h time points. [¹⁴C(U)]C₆₀ and [¹⁴C(U)]C₆₀‐retinol were detected in liver of rats and together accounted for ~99% and ~56% of the total recovered at 1 and 30 days postexposure, respectively. The blood radioactivity at 1 h after [¹⁴C(U)]C₆₀ exposure was fourfold higher in rats than in mice; blood radioactivity was still in circulation at 30 days post [¹⁴C(U)]C₆₀ exposure in both species (<1%). Levels of oxidative stress markers increased by 5 days after exposure and remained elevated, while levels of inflammation markers initially increased and then returned to control values. The level of cardiovascular marker von Willebrand factor, increased in rats, but remained at control levels in mice. This study demonstrates that [¹⁴C(U)]C₆₀ is retained in female rodents with little elimination by 30 days after i.v. exposure, and leads to systemic oxidative stress. Copyright © 2015 John Wiley & Sons, Ltd.     

Metabolic disposition and irreversible binding of phencyclidine in rats

The metabolic disposition of [¹⁴C]phencyclidine ([¹⁴C]PCP) was examined in rats after intratracheal, ip or iv drug administration. [¹⁴C]PCP absorption by the lung was related to time biphasically after intratracheal administration. At 1 hr after ip administration of [¹⁴C]PCP (1.8 mg/kg), the concentration of radioactivity in various tissues decreased (in descending order) in the liver, fat, kidney, lung, testes, spleen, heart, and brain. High levels of radioactivity were also detected in the urine and feces, but not in the blood. The radioactivity accumulated by the liver, lung, and kidney was only partially removed by repeated extraction with 80% methanol, indicating the in vivo formation of PCP reactive metabolite which bound with protein irreversibly. Incubation of [¹⁴C]PCP with rat liver microsomes corroborated that a PCP reactive metabolite was formed. Although hepatic benzpyrene hydroxylase activity decreased significantly after rats were pretreated with PCP, neither microsomal cytochrome P-450 content nor aniline hydroxylase and p-chloro-N-methyl-aniline demethylase activities in lung, liver, and kidney were altered. After a single iv dose of [¹⁴C]PCP (0.9 mg/kg), biliary radioactivity peaked at about 30 min. Hydroxylated PCP and corresponding glucuronides represented the bulk of the biliary radioactivity. When radioactive bile from a rat pretreated with [¹⁴C]PCP was administered to a recipient rat intragastrically, radioactivity was found in the bile, indicating enterohepatic recycling of PCP.     

Studies on the Metabolism of d-Limonene (p-Mentha-1,8-diene): I. The Absorption,Distribution and Excretion of d-Limonene in Rats

Abstract

1. The absorption, distribution and excretion of d-limonene were investigated in rats using the ¹⁴C-labelled compound.

2. The highest concentration of radioactivity in blood was obtained 2 h after oral administration of [¹⁴C]d-limonene and most occurred in the serum fraction. Radioactivity in the tissues reached maximum 1 or 2 h after administration. Radioactivity in liver, kidney and blood was higher than in other tissues, but was negligible 48 h after administration. An autoradiographic study confirmed these findings of tissue distribution.

3. About 60% of administered radioactivity was recovered from urine, 5% from faeces and 2% from expired CO₂ within 48 h. In bile duct cannulated rats, about 25% of the dose was excreted in bile within 24 h.     

Biological fate of sulphur mustard in rat: toxicokinetics and disposition

1. The toxicokinetics of sulphur mustard were studied after i.v. administration (10mg/kg) to rat.

2. After i.v. administration, blood concentrations of sulphur mustard were best described by a two-compartment model with distribution and elimination half-lives of 5–6 min and 3–59 h, respectively. The apparent volume of distribution at steady state (V_dss) was 74–41/kg and total body clearance (Cl) was 211/hkg^?1.

3. Unchanged sulphur mustard was still detectable in the systemic circulation 8 h after administration. Appreciable and long (96 h) accumulation of ¹⁴C was found in the systemic circulation, and significant high affinity of ¹⁴C-sulphur mustard for red blood cells.

4. The disposition of ¹⁴C was also investigated after i.v. injection of ¹⁴C-sulphur mustard to rat. Urine was the major route of excretion of sulphur mustard and/or its metabolites. Of the administered radioactivity 80% was excreted in urine over 96 h, the greater part in the first 24 h after administration. Residual ¹⁴C continued to be excreted until 4 days later. In urine, no sulpho- or glucuronyl-conjugates were detected. Of dose < 3% was recovered in faeces.