Following a single oral dose

Administration of dibutyltin dichloride intraperito-neally to rats led to the formation of butyl(3-hydroxy-butyl)tm, butyl(4-hydroxybutyl)tin, and monobutyltin. The major metabolite (buty 1(3-hydroxybutyl)tin) was distributed to the kidney at a relatively high concentration compared with the other metabolites, and its concentration increased with time. Butyl(4-hydroxybutyl)tin was found in urine only. The parent compound and other metabolites were detected in the brain (Ishizaka et al., 1989). Dibutyltin diacetate was destarmylated by 14% within 90 h following a single oral dose in mice at 1.1 mg/kg body weight, with several butyltin derivatives found in the liver or faeces (Boyer, 1989). 

Table III. Tissue Distribution in Dams Following a Single Oral Dose of 200 /Ag/kg of C -2,3,7,8-Tetrachlorodibenzo- >-Dioxin on Gestation Day 16, 17, or 18 (/ g/gram of tissue)...

The percentage of the total dose of radioactivity excreted daily in the feces, urine, or expired air over a 21-day period following a single oral dose of TCDD- C is shown in Figure 2. Approximately 30% of the... 

Figure 2. Excretion of activity by rats following a single oral dose of 50 fJig/kg (0.14 iCi/kg) 2,3J,8-tetra-chlorodibenzo-p-dioxin. Each point represents the mean SE for three rats.

Table II. Activity Expressed as Percent of Dose per Gram (%/gram) in Various Tissues of Rats 3, 7, and 21 Days Following a Single Oral Dose of TCDD- C ...

In this study the tissue distribution and excretion of activity has been evaluated in rats following a single oral dose of TCDD- C. Almost 30% of the dose administered was eliminated via the feces during the first 48 hours following treatment. The excretion of activity via the... 

The dose of TCDD given to the male rats used in this study, 50 />tg/kg, was approximately twice the LD50, 23 /xg/kg. This large dose was necessary because of the low specific activity of the TCDD- C used. In this study rats lost weight, and their physical condition was poor, which typifies the insidious response to TCDD (J). Survival of the rats for 21 days was not totally unexpected because in previous studies on the lethality of TCDD deaths frequently occurred 20 or more days following a single oral dose of similar magnitude (I). With doses that do not induce untoward effects, the compound may be excreted at a different rate. 

Compound (1) suffered from an unfavorable pharmacokinetic profile when studied in rats. It is cleared very rapidly from rat plasma (half-life, t 2 — 0.4/z) and is poorly bioavailable F — 2%), as reflected by the low plasma concentration (area under the plasma concentration-time curve, AUCo oo = 0.2pMh) following a single oral dose of 25mg/kg in rats [42]. The main challenge was to further optimize this series to obtain NS3 protease inhibitors with low-nanomolar cell-based potency (EC5q< 10 nM) and with an adequate pharmacokinetic profile for oral absorption. 

Fig. 21 Comparison of mean blood serum levels obtained with chloramphenicol palmitate suspensions containing varying ratios of A and B polymorphs, following a single oral dose equivalent to 1.5 g of chloramphenicol. Percentage of polymorph B in the suspension M, 0% N, 25% O, 50% P, 75% L, 100%. (From Ref. 37.).

Acute oral toxicity To determine the potential acute toxicity-lethality following a single oral dose... 

The use of cholestyramine in reducing the body burden of chlordecone has been investigated in humans and rats. In the human study, 32 workers who had been heavily exposed to chlordecone over a period of from 3 to 16 months were treated for 5 months with cholestryramine (Cohn et al. 1978). Cholestyramine treatment resulted in a sevenfold increase in the fecal excretion of chlordecone. Similarly, a study using rats demonstrated a doubling of fecal excretion and a 30--50% decrease in tissue levels of chlordecone after 2 weeks treatment with cholestyramine following a single oral dose of chlordecone (Boylan et al. 1978). 

Following a single oral dose of 2,000 mg/kg of di-/ -ocLylphthalatc in rats, mono- -octylphthalate was detected in blood with peak levels observed at 3 hours and in the testes with peak levels observed at 6 hours (Oishi 1990). The biological half-life and mean residence time of mono-w-octylphthalate in blood were 3.3 and 5.4 hours, respectively. After 13 weeks of oral exposure of rats to di-w-octylphthalate in the diet at concentrations up to 5,000 ppm (350 and 403 mg/kg/day in males and females, respectively), the livers contained di -/ -oc1y lphthalate residues that were either below or just slightly above the detection limit (<3 ppm) (Poon et al. 1995). The adipose tissue of rats fed 5,000 ppm showed di-/ -octylphthalate residue levels of 15 ppm (males) and 25 ppm (females). This study is limited in that it did not analyze tissues for the presence of metabolites. 

Wilkinson JM, Pollard I. (1993). Accumulation of theophylline, theobromine, and paraxanthine in the fetal rat brain following a single oral dose of caffeine. Brain Res Dev Brain Res. 75(2) 193-99. Winstock AR, Trivedy CR, Warnakulasuriya KAAS, Peters TJ. (In press). A dependency syndrome related to areca nut use some medical and psychological aspects among areca nut users in the Gujarat community in the UK. Addict Biol. 

Cell proliferation, predominantly in the proximal tubules, occurred in Wistar rats following a single oral dose of 100 mg/kg 1,2-dibromoethane in corn oil. Mitotic activity peaked at 30 hours. Lack of any histologic evidence of tubular necrosis between 8-48 hours after treatment indicates that such proliferation was not a regenerative response (Ledda-Columbano et al. 1987b). 

Peak clinical effect following a single oral dose, except where indicated. Duration of action is frequently dose-dependent. 

Excretion - Fecal excretion was the major route of elimination following a single oral dose of 360 mg orlistat in healthy and obese subjects. Orlistat and... 

Mean systemic clearance in healthy adult volunteers following a single oral dose was... 

Following a single oral dose of 15 to 25 mg/kg, ethambutol attains a peak of 2 to 5 mcg/mL in serum 2 to 4 hours after administration. Serum levels are similar after prolonged dosing. The serum level is undetectable 24 hours after the last dose except in some patients with abnormal renal function. 

Metabolism/Excretion - Following a single oral dose of tenofovir, the terminal elimination half-life is approximately 17 hours. Tenofovir is eliminated by a combination of glomerular filtration and active tubular secretion. 

Table II. Radioactivity levels In tissues of rats following a single oral dose of 2 mg/kg C-phosfolan.

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