15 Multiple dosing studies showed little to modest accumulation of raltegravir.
In multiple dosing studies two colorectal cell lines (Mawi and LS174T) were treated with temozolomide or BCNU at 24 h intervals for up to 5 days, with or without either 100 microM O 6 -BG fO 6 -BGor 1 microM O(6)-BG for 24 h, commencing 1 h before alkylating treatment.
Therefore the present subacute (28-day) study was carried out to evaluate a multiple dose study design and to compare the results with the common OECD design.
A selected formulation given once‐daily was further evaluated against the commercial enteric tablet dosed twice‐daily in a multiple dose study, and shown to provide desired nearly constant therapeutic plasma concentrations over the entire 24‐h dosing interval.
Considering these challenges, we developed a general nanosuspension formulation that minimized organic co-solvent, was easy to prepare and was applicable to an IV infusion or multiple dose study.
To validate this hypothesis and the therapeutic potential of the LNA ASO, a multiple dose study with weekly dosing of 5 mg/kg of the 13-mer LNA antisense oligonucleotide was conducted.
The phase I trial was an open-label, single and multiple dose study, with accelerated, toxicity-guided dose escalation [ 26].
Although baseline cortisol levels remained normal, all patients treated at 500 and 800 mg in the multiple dose study developed an abnormal response to a short Synacthen test by Day 11.
Furthermore, it was assumed that variability would be similar to that seen in preliminary data from the apixaban human ascending multiple dose study, i.e. that the intra-subject SD for log Cmax and logAUC 0,∞) would not be greater than the inter-subject SD of 0.19 and 0.20 calculated for log Cmax and logAUC 0,τ), respectively [ 30].
These were GCP-compliant, single and multiple dose studies of PK/PD and tolerability in healthy volunteers and postmenopausal women.
The maximum tolerated dose of 6 mg/kg drisapersen was identified for further characterization in multiple dose studies in the non-ambulant DMD population.
