Dosing period

How did you feel just before the dose, and during the dosing period ... 

Monitoring parameters Observe for anaphylaxis during first dose Periodic renal and hematologic function tests with prolonged therapy fever, mental status, WBC count... 

Brain lead levels had also increased. No accumulation of lead was observed in the lungs, heart, stomach, or spleen over the dosing period. Rat pups (4-8 weeks old) had a 2-3-fold increase in brain lead concentration when oral doses increased by 10-fold from 0.1 to 1 mg lead/kg (Collins et al. 1982). The highest brain lead level in these pups was in the hippocampus. 

A 3-week study of MK-0822 (0.5, 2.5 and 10 mg qd) in post-menopausal women showed a 70-80% reduction in serum CTx at the top dose and an 80% reduction in urinary NTx at both the 2.5 and 10 mg doses [74]. The compound was safe and well-tolerated throughout the dosing period. 

The dosing period of the pregnant animals during studies on embryonic development (traditional Segment II studies) has been standardized. 

Finally, any effects present at the end of the dosing period may be investigated during the following recovery period in which a proportion of the animals showing effects are retained undosed while recovery is monitored. Recovery periods of 2 weeks or 1 month are t)q)ical. These may not be sufficient to demonstrate complete recovery. However, signs of reversibility should be taken into accoimt when making a risk assessment. 

The first consideration, as always, will be safety information that can be obtained more safely in healthy subjects, which may subsequently reduce risk to patients, should prompt a debate on whether it is wise to progress according to plan or whether an additional study should be performed in healthy subjects. Another option that may be considered is to proceed with the planned study in patients but to admit them to hospital or a clinical investigation unit for all or part of the dosing period. However, this might not be feasible because suitable facilities and staff are not available or because the anticipated rate of patient recruitment might be considered unacceptably slow. 

Androderm - Following application to nonscrotal skin, testosterone is continuously absorbed during the 24-hour dosing period. Daily application of 2 systems at approximately 10 00 p.m. results in a serum testosterone concentration profile that mimics the normal circadian variation observed in healthy young men. Maximum concentrations occur in the early morning hours with minimum concentrations in the evening. 

The majority of rashes associated with nevirapine occur within the first 6 weeks of initiation of therapy. Instruct patients not to increase the 200 mg/day (4 mg/kg/day in children) dosage if any rash occurs during the 2-week lead-in dosing period until the rash resolves. 

Animals should be weighed on day 0. .., on the first day of dosing, at least every 3 days during the dosing period and on the day of scheduled kill. Food consumption should be recorded at 3-day intervals and should coincide with days of body weight determination (4). 

All animals are observed for clinical condition. Observations should be made at least once daily prior to commencement of dosing. During the dosing period, the animals should be observed... 

The dosing period (at least between days 6 and 17 post-coitum) and the maternal observations are the same as those intended for the main study. 

Maternal morbidity/mortality, clinical condition, body weight, and food consumption are monitored throughout the study. Typically, the dams are observed at the beginning and end of each working day for morbidity/mortality and at least once after each dose administration to detect any abnormalities in appearance or behavior. Body weight and food intake are usually recorded twice weekly, at least throughout the dosing period. 

A typical full teratology study in the mouse is comprised of 100 dams divided across four groups (three treated plus one control) with the aim of attaining at least 16 litters per group for evaluation. The dosing period (at least between days 6 and 15 post-coitum) and the maternal observations are the same as those described for a dose range-finding study. 

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