Примери за използване на Therapeutic exposure на Английски и техните преводи на Български
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No effects were noted at 14-times the human therapeutic exposure.
The radiation dose resulting from therapeutic exposure may result in higher incidence of cancer and mutations.
No effects were observed at 3times the human therapeutic exposure.
At two-fold systemic exposure compared to maximum human therapeutic exposure, there was an increase in postimplantation loss, decrease in the pup birth weights, and reduction in pup survival during the first three days of lactation in rats.
The NOAEL was 21 times(at Day 21 post partum) and 2.3 times(Day 69 post partum) the human therapeutic exposure, respectively.
In animal studies at systemic plasma exposures(AUC)to amprenavir lower than therapeutic exposure in patients treated with Telzir, some developmental toxicity was observed(see section 5.3).
Larotrectinib had no effect on respiratory function in rats; at exposures(Cmax)at least 8-times the human therapeutic exposure.
In the single-dose dog infusion studies,1.0 mg/ kg(6 fold the recommended human therapeutic exposure based on AUC) administered over 15 minutes was well tolerated with no renal effects.
Cabozantinib was not carcinogenic in the rasH2 mouse model at a slightly higher exposure than the intended human therapeutic exposure.
In the single-dose dog infusion studies,1.0 mg/kg(6 fold the recommended human therapeutic exposure based on AUC) administered over 15 minutes was well tolerated with no renal effects.
Reduced acoustic startle response was observed in juvenile rats 1-2 weeks after exposure at>2 times the human therapeutic exposure.
These findings were generally observed at systemic exposure levels within the range of therapeutic exposure or above, with the exception of the findings in rats, which occurred below therapeutic exposure due to a high tissue distribution.
At adult age(Day 69 post partum), no effects of bosentan were detected at 1.3(males)and 2.6(females) times the therapeutic exposure in children with PAH.
High doses of palonosetron(each dose causing at least 30 times the human therapeutic exposure) applied daily for two years caused an increased rate of liver tumours, endocrine neoplasms(in thyroid, pituitary, pancreas, adrenal medulla) and skin tumours in rats but not in mice.
Following inhalation the systemic exposure based on AUC values in rats exceeded the corresponding therapeutic exposure in human patients by approximately 13 times.
In 3 month studies, evidence of liver toxicity, including elevated enzymes and morphologic alterations,was observed in both rats and monkeys at doses 4- to 6-fold higher than the anticipated clinical therapeutic exposure.
Radioactive Sm-EDTMP has not been tested for mutagenicity/ carcinogenicity butdue to the radiation dose resulting from therapeutic exposure it should be regarded as presenting a genotoxic/ carcinogenic risk.
Adverse reactions not observed in clinical studies, but seen in animals at exposure levels similar to clinical exposure levels and with possible relevance to clinical use were as follows: nelarabine caused histopathological changes to the central nervous system(white matter vacuolation and degenerative changes in cerebrum, cerebellum and spinal cord) of monkeys after daily treatment withnelarabine for 23 days, at exposures below the human therapeutic exposure.
Two-year carcinogenicity studies with erlotinib conducted in rats andmice were negative up to exposures exceeding human therapeutic exposure(up to 2-fold and 10-fold higher, respectively, based on Cmax and/or AUC).
The systemic exposure to lopinavir/ ritonavirat the maternal and developmental toxic dosages was lower than the intended therapeutic exposure in humans.
Firstly, since the TCC metabolite M2 has been shown to be aneugenic at exposure levels close to human therapeutic exposure, the CHMP considered that the dose should be restricted(to 8 mg bid PO and 4 mg bid by IM) and long-term use avoided.
In rats, opicapone did not affect male and female fertility orprenatal development at exposure levels 22 times the therapeutic exposure in humans.
In rabbits, embryonic development was adversely affected and the incidence of gallbladder agenesis or small gallbladder was increased at doses of 300 and500 mg/kg(approximately 24 and 28 times the human therapeutic exposure with a maximum recommended nateglinide dose of 180 mg, three times daily before meals), but not at 150 mg/kg(approximately 17 times the human therapeutic exposure with a maximum recommended nateglinide dose of 180 mg, three times daily before meals).
Safety margins adapted for IP receptor potency for the active metabolite were 2-fold(based on total exposure) in relation to human therapeutic exposure.
Renal tolerability of zoledronic acid was established in rats when given 0.6 mg/kg as 15-minute infusions at 3-day intervals,six times in total(for a cumulative dose that corresponded to AUC levels about 6 times the human therapeutic exposure) while five 15-minute infusions of 0.25 mg/kg administered at 2-3-week intervals(a cumulative dose that corresponded to 7 times the human therapeutic exposure) were well tolerated in dogs.
However, no effects on general development, growth, sensory, cognitive function and reproductive performance were detected at 7(males) and 19(females)times the human therapeutic exposure at Day 21 post partum.
Subchronic and chronic toxicity In the intravenous infusion studies, renal tolerability of zoledronic acid was established in rats when given 0.6 mg/ kg as 15-minute infusions at 3-day intervals,six times in total(for a cumulative dose that corresponded to AUC levels about 6 times the human therapeutic exposure) while five 15-minute infusions of 0.25 mg/ kg administered at 2- 3-week intervals(a cumulative dose that corresponded to 7 times the human therapeutic exposure) were well tolerated in dogs.