Loading Dose Group Research Articles

INITIAL LOADING (400 μg TWICE DAILY) VERSUS STATIC (400 μg NOCTE) DOSE BUDESONIDE FOR ASTHMA MANAGEMENT

SUMMARY This double‐blind study aimed to determine whether superior asthma control is achieved with budesonide (Pulmicort® Turbohaler®) at a loading dose (LD) (400 μg b.d.) for 6 weeks, followed by step down to 400 μg nocte for 12 weeks, compared with a static dose (SD) (400 μg nocte) for 18 weeks. A total of 682 patients (mean peak expiratory flow rate (PEFR) 413 l/min), who demonstrated ≥15% reversibility in PEFR, were randomised into the study. After 18 weeks, patients experienced improvements in morning PEFR (+45 l/min, both groups), symptom score (LD ‐0.57, SD ‐0.49, on a scale of 0‐3), sleep disturbance (LD ‐1.21 nights/week, SD ‐1.06 nights/week) and to‐agonist use (LD ‐1.36 puffs/day, SD ‐1.06 puffs/day), within both groups (each p=0.0001). At 18 weeks, 82% (LD) and 84% (SD) of patients benefited from no nocturnal wakening in the previous 7 days. Overall, at 18 weeks, asthma control was not significantly different between the groups. After 6 weeks, improvements in morning PEFR (LD +36 l/min, SD +26 l/min) and β2‐agonist use (LD ‐1.10 puffs/day, SD ‐0.94 puffs/day) were greater in the loading dose than in the static dose group (each p<0.05). The greater improvement in morning PEFR in the loading dose group was significant by day 7 (p<0.05). While both regimens are equally effective in achieving asthma control at 18 weeks, early clinical advantage is gained with initial loading dose budesonide (400 μg b.d.).

Prospective, Randomized, Controlled Evaluation of a Gentamicin Loading Dose in Neonates

A prospective, randomized, controlled evaluation comparing a 4-mg/kg loading dose (LD) of gentamicin to the standard regimen of 2.5 mg/kg every 12, 18 or 24 h was conducted in critically ill neonates. The objective of the study was to compare the time required to achieve a therapeutic peak serum concentration (i.e. the number of dosing intervals) and to compare the number of serum concentrations outside the therapeutic range as an indicator of potential toxicity between the treatment groups. Eighteen of 26 patients, 5 of 13 in the control group and 13 of 13 in the LD group (p = 0.012) achieved an initial peak concentration of > or = 5 micrograms/ml following the first gentamicin infusion. There were no significant differences between the control and LD group in the number of potentially toxic serum concentrations. When patients were subdivided according to gestational age (GA), patients of < or = 34 weeks had significantly lower initial peak concentrations. A LD of 4 mg/kg in neonates, particularly those of < or = 34 weeks GA, produced a therapeutic peak concentration following the initial dose. There is a minimal risk of attaining serum concentrations commonly associated with toxicity providing the dosage interval is adjusted based on serum creatinine determinations. Based on this study, infants of > 34 weeks GA generally achieve therapeutic peak concentrations after the first dose with conventional dosing; however, in younger infants an appropriate LD is required to reach therapeutic concentrations early in therapy.

Adjusting the loading dose of magnesium sulfate for tocolysis

The purpose of this prospective study was to establish a method to calculate a loading dose of magnesium sulfate so as to achieve therapeutic levels of tocolysis more quickly. Fifty patients in preterm labor were enrolled. In the first phase 25 patients were studied so that the apparent volume of distribution for the loading dose of magnesium sulfate could be estimated and an adjusted loading dose could be calculated. The efficacy of this adjusted loading dose was then tested on a further 25 patients in the second phase. We found that the apparent volume of distribution could be accurately estimated and an adjusted loading dose calculated, with the use of ideal body weight, degree of underweight, and current use of (β-sympathomimetics. In the adjusted loading dose group therapeutic levels were achieved more often, with higher postloading magnesium levels and a greater decrease in contraction index immediately after the loading dose. We conclude that an adjusted loading dose can be calculated for magnesium sulfate to optimize tocolytic therapy.

Volume of Distribution of Theophylline in Acute Exacerbations of Reversible Airway Disease: Effect of Body Weight

The literature is unclear as to whether theophylline loading doses should be based on total body weight (TBW) or ideal body weight (IBW). The objective of this study was to determine the most appropriate body weight for estimation of volume of distribution (Vd) in calculating theophylline loading dose in patients with acute bronchospasm. Fifty-four adult patients with acute bronchospasm requiring intravenous (IV) theophylline therapy were entered into the study. Patients were randomized into three theophylline loading dose groups based on (1) TBW, (2) IBW, and (3) adjusted body weight (ABW). Initial serum theophylline concentrations were used to determine an IV loading dose to reach a plasma concentration of 12 to 15 micrograms/ml. Percent prediction error was used to determine the appropriateness of each dosing group. Volumes of distribution were also determined for each group. There was a statistically significant difference at p less than 0.01 in the percent prediction error when patients in the TBW group were compared to the IBW and ABW groups. A statistically significant difference in the Vd was observed between the TBW and IBW group (p less than 0.01). We conclude that IBW is more appropriate than TBW or ABW for determining theophylline loading dose in patients with acute bronchospasm.