Oral repeated dosing

No oral repeat dose studies or human evidence are available and therefore no classification is Inhalation... 

Kobayashi R, Ohno H, Jindo T, et al. 1997a. Fifty-two-week oral repeated dose toxicity study in rats with ebselen. Yakuri to Chiryo 25(Suppl.) 41-58. 

If patient vomits within 2 hours of administration, repeat dose orally or intravenously. 

Methadone has oral efficacy, extended duration of action, and ability to suppress withdrawal symptoms in heroin addicts. With repeated doses, the analgesic duration of action of methadone is prolonged, but excessive sedation may also result. Although effective for acute pain, it is usually used for chronic cancer pain. 

Disulfoton induced the liver MFO system in animals (Stevens et al. 1973). In the same study, exposure to disulfoton orally for 3 days also increased ethylmorphine N-demethylase and NADPH oxidase activities, but had no effect on NADPH cytochrome c reductase. Thus, the induction of the MFO system required repeated dosing with relatively high doses. Furthermore, these changes are not specific for disulfoton exposure, and these subtle liver effects require invasive techniques in humans to obtain liver tissue for performance of these enzyme assays. 

The pharmacokinetics of ondansetron in man have been determined in healthy volunteers after single and repeat doses [84]. The clinical pharmacokinetics (Table 7.8) showed many similarities with the kinetics in animals, but also some important differences. Elimination is rapid, but less so than in animals. The volume of distribution is similar in animals and man. As in animals, the clearance of ondansetron in man is predominantly by metabolism. However, metabolic clearance in man is considerably lower than in animals, resulting in a lower first-pass metabolism and a significantly greater oral bioavailability of 60 %. Steady-state concentrations of ondansetron are consistent with the single-dose kinetics of the compound and show no evidence of significant accumulation. 

The commercial HBCD has shown low acute toxicity [6]. The minimum lethal dose is greater than 20 g/kg for dermal and oral administration [18]. Repeated dose toxicity was assessed by Van der Ven et al. [42] and revealed enhanced endocrine... 

Morphine antagonists and partial agonists. The effects of opioids can be abolished by the antagonists naloxone or naltrexone (A), irrespective of the receptor type involved. Given by itself, neither has any effect in normal subjects however, in opioid-dependent subjects, both precipitate acute withdrawal signs. Because of its rapid presystemic elimination, naloxone is only suitable for parenteral use. Naltrexone is metabolically more stable and is given orally. Naloxone is effective as antidote in the treatment of opioid-induced respiratory paralysis. Since it is more rapidly eliminated than most opioids, repeated doses may be needed. Naltrexone may be used as an adjunct in withdrawal therapy. 

Repeated Dose 28-day Oral Toxicity Study in Rodents (Updated Guideline, adopted 27 July 1995)... 

Repeated dose 28-day oral toxicity smdy in rodents (July 20(X))... 

B.26 Sub-Chronic Oral Toxicity Test Repeated Dose 90-Day Toxicity Study in Rodents (2001)... 

The combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD TG 422) is, for the repeated dose toxicity part, concordant with the standard 28-day oral toxicity study (OECD TG 407) except for use of pregnant females and longer exposure duration (about 6 weeks for males and approximately 54 days for females) in the combined study compared to the standard 28-day study. 

Repeated dose 90-day oral toxicity study in rodents... 

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