Clinical therapeutics
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Clinical therapeutics · May 2008
ReviewRotigotine transdermal system for the treatment of Parkinson's disease.
Levodopa has been the cornerstone of the treatment of Parkinson's disease (PD) for >30 years, but long-term levodopa therapy is associated with development of such motor complications as motor fluctuations, dyskinesias, and drug-induced involuntary movements. Rotigotine is a dopamine agonist with high affinity for the D(2) receptor. Rotigotine transdermal system, the first such system approved by the US Food and Drug Administration for the management of PD, has been formulated to deliver a consistent concentration of drug to the bloodstream with the goal of minimizing the complications associated with pulsatile dosing. ⋯ The available evidence suggests that rotigotine transdermal system was effective compared with placebo in decreasing morbidity in patients with early and advanced PD. The most commonly reported adverse events associated with rotigotine transdermal system were application-site reaction, nausea, and somnolence. Additional clinical trials are needed to determine the long-term tolerability profile of rotigotine transdermal system and its clinical efficacy and tolerability compared with oral dopamine agonists.
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Clinical therapeutics · May 2008
In vitro stability of two formulations of recombinant activated factor VIIa reconstituted in inappropriate solvents or at inappropriate volumes.
Recombinant activated factor VIIa (rFVIIa) is indicated for on-demand treatment of bleeding and the prevention and treatment of surgical bleeding in patients with hemophilia A or B who have antibodies to coagulation factors VIII or IX. The currently approved single-use formulation of rFVIIa is freeze dried and is stable for up to 3 years when stored at 2 degrees C to 8 degrees C (36 degrees F-46 degrees F). A new formulation has been developed that is stable for up to 2 years when stored at temperatures up to 25 degrees C (77 degrees F). This formulation does not require refrigerated storage and does not have to be brought to room temperature before use. Both formulations must be reconstituted before use. The original formulation is reconstituted with sterile water for injection (SWFI), whereas the new formulation is reconstituted with a solvent containing histidine. ⋯ Based on the results of these experiments, the 2 rFVIIa products should be reconstituted using the appropriate solvent at the correct volume.
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Clinical therapeutics · Apr 2008
Randomized Controlled Trial Comparative StudyCombination therapy versus monotherapy as initial treatment for stage 2 hypertension: a prespecified subgroup analysis of a community-based, randomized, open-label trial.
Current guidelines suggest consideration of initial combination therapy for patients with stage 2 hypertension, but rates of hypertension treatment and control in clinical practice vary according to age, race, sex, and body mass index (BMI). ⋯ Across various subgroups of patients with stage 2 hypertension, combination therapy was consistently associated with a significantly greater reduction in SBP than monotherapy. With the exception of a significantly greater increase in dizziness compared with monotherapy, combination therapy was well tolerated.
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Clinical therapeutics · Apr 2008
Randomized Controlled Trial Comparative StudyPharmacokinetics of single-dose and multiple-dose memantine in healthy chinese volunteers using an analytic method of liquid chromatography-tandem mass spectrometry.
This study consisted of 2 phases: development of a liquid chromatography-tandem mass spectrometry (LC/MS) method for determination of memantine in human plasma and characterization of single-dose and multiple-dose pharmacokinetic profiles of memantine in healthy Chinese volunteers using the LC/MS method. ⋯ In these healthy Chinese subjects, the t(1/2) and MRT values were fixed and did not increase following the increased dose, and the AUC(infinity) and C(max) values increased following the increasing dosage of memantine. Linear pharmacokinetics was found at doses from 5 to 20 mg. The multiple-dose pharmacokinetic parameters (other than C(max)) were nearly similar compared with the single-dose administration. The maximum plasma concentration of memantine after multiple-dose administration was greater than that after a single-dose administration, suggesting memantine accumulation with multiple-dose administration of 5 mg and requiring further confirmation in larger studies.
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Clinical therapeutics · Apr 2008
Randomized Controlled Trial Multicenter Study Comparative StudyEffects of carvedilol on left ventricular function and oxidative stress in infants and children with idiopathic dilated cardiomyopathy: a 12-month, two-center, open-label study.
This study was conducted to determine the effects of carvedilol adjunct to standard treatment on left ventricular function (LVF), estimated as ejection fraction (EF) and fractional shortening (FS) on echocardiography, in children with idiopathic dilated cardiomyopathy (DCM). A secondary end point was to characterize the antioxidant potential of carvedilol. ⋯ These pediatric patients with DCM treated for 12 months with carvedilol (up to 0.8 mg/kg/d in children