Single-dose trials

Rosenthal, D.I. et al. (1999) A phase I single-dose trial of gadolinium texaphyrin (Gd-Tex), a tumor selective radiation sensitizer detectable by magnetic resonance imaging, Clin. Cancer Res. 5, 739-745. 

G. lamblia is treated with 5-nitroimidazole derivates. Paromomycin is a second choice in specific circumstances (e.g. pregnancy). In a Cochrane review, where 34 trials were included and where only one trial was without significant methodological flaws, the authors concluded that a single dose of tinidazole can provide the highest clinical cure rate with relatively few adverse effects. The high recun ence rate of disease after initial diug therapy is a problem. 

The single-dose toxicity studies were performed in two mammalian species, rat and mouse, by the route used in clinical practice, that is oral, as well as that ensuring adequate systemic exposure to the drug, that is intravenous. The subacute (3 months) toxicity studies were correctly carried out in the two animal species (rat, dog) in which also the pharmacokinetics was studied. Since in accordance with the International Conference on Harmonization (CPMP/ICH/286/95), 3-month toxicity studies support clinical trials for up to 1 month s duration (the longest duration of drug administration in clinical use), chronic toxicity studies have not been performed. 

The initial strategy for Phase I is to conduct a single-dose safety study in normal volunteers. The first trial demands close 24-hour supervision in a clinical setting. Ethical considerations may, however, demand that only patients be used, for example, when evaluating an anticancer agent with predictable toxicity. A repeat dose tolerance and pharmacokinetic study in normal or patient volunteers is then conducted for chronically administered drugs. These studies will provide the necessary safety information to support efficacy testing. 

In the United States, as an alternative to 2-week studies, single dose toxicity studies with extended examinations can support single dose human trials. 

Kerb R, Brockmoiier J, Staffeldt B, Ploch M, Roots I. (1996). Single-dose and steady-state pharmacokinetics of hypericin and pseudohypericin. Antimicrob Agents Chemother. 40(9) 2087-93. Kim HL, Streltzer J, Goebert D. (1999). St. John s wort for depression a meta-analysis of well-defined clinical trials. J Nerv Ment Dis. 187(9) 532-38. 

Hanks GW, O Neill WM, Simpson P, Wesnes K. (1995). The cognitive and psychomotor effects of opioid analgesics II. A randomized controlled trial of single doses of morphine, lorazepam, and placebo in healthy subjects. EurJ Clin Pharmacol. 48(6) 455-60. 

This reversible HDAC inhibitor has potency in low nanomolar ranges. ° TSA induces cellular differentiation, apoptosis and growth factor unresponsiveness when administered under regimental dosing and not under single dose administration. However, TSA showed poor results in clinical trials, likely due to a combination of poor biodistribu-fion and fast metabolism. 

A preliminary assessment of the effect of food on pharmacokinetics can generally be studied in a single-dose, two-arm, randomised, crossover design. Preliminary information can often be obtained by including a fed occasion in the first, dose-escalating study. This will be insuffi-cent for registration purposes, which require an adequately powered study performed with the final formulation, but the information should be sufficient to indicate whether there is need for restrictions on dosing relative to meals in repeat-dose studies in healthy volunteers and patient clinical trials. 

Monotherapy-The usual starting dose of rosiglitazone is 4 mg, administered either as a single dose once daily or in divided doses twice daily. In clinical trials, the 4 mg twice-daily regimen resulted in the highest reduction in FPG and HbA-ic-... 

Hypertension - Initiate therapy with a single dose of 25 mg/day Thalitone, 15 mg). If response is insufficient after a suitable trial, increase to 50 mg Thalitone, increase from 30 to 50 mg). For additional control, increase dosage to 100 mg once daily (except Thalitone), or add a second antihypertensive. 

Orally disintegrating tablets - A single dose of 2.5 mg was effective for the acute treatment of migraines in adults. If the headache returns, the dose may be repeated after 2 hours, not to exceed 10 mg within a 24-hour period. Trials have not adequately established the efficacy of a second dose if the initial... 

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