Physicians should give AED polytherapy only when the maximum therapeutic doses of monotherapy are ineffective.
Of those on PPI therapy for a one-year continuous period, the majority 34,589 (95%) continued on maximum therapeutic dose.
As a result, the maximum therapeutic dose which can be given and, therefore, the maximum anti-cancer effect these agents can exert is restricted.
Indeed, there was no increase in hepatic toxicity in alcoholic patients who were given the maximum therapeutic dose of paracetamol (4 g/day) [29].
The SP864 study demonstrated dose-proportional pharmacokinetics of rotigotine at steady state in patients with advanced PD (n = 66) from 8 mg/24 h rotigotine to the maximum therapeutic dose of 16 mg/24 h, and supratherapeutic doses of 20 and 24 mg/24 h [ 33].
The analysis of the HSE-PCRS pharmacy claims database indicated that the majority of patients on long term PPI therapy were continuously prescribed maximum therapeutic dose; costs were potentially reduced by one quarter with use of step down therapy.
Use of PPIs at maximum therapeutic dose for > 8 weeks (38,153 patients, 3.7%) was the third most common PIP, whilst alpha blockers with long-term urinary catheter in situ (31,226 patients 3.1%) was next.
The most common PIP issues were use of PPIs at maximum therapeutic dose for > 8 weeks (3.7%, 38,153 patients), NSAIDs for > 3 months (3.2% 32,373 patients), and use of long-term neuroleptics (2.1%, 21,012 patients.
In a murine L1210 tumour model, for example, no long-term survivors were seen in animal groups treated with free drug, whereas at the maximum therapeutic dose of liposomal mitoxantrone survival rates of 40% were observed.
The dose range of lesogaberan that was used in this study was comprehensive in that it encompassed doses both higher and lower than the 65 mg dose used in previous studies in patients with GERD and in patients with GERD who had persistent reflux symptoms despite PPI treatment [ 14, 20], as well as including a maximum therapeutic dose of 240 mg.
