RESUMEN
PURPOSE: Methylphenidate hydrochloride extended-release chewable tablet (MPH ERCT) is approved for treatment of attention deficit hyperactivity disorder in patients aged 6 years and older. This article evaluates the pharmacokinetic parameters and relative bioavailability of MPH ERCT when chewed versus swallowed whole. METHODS: In this open-label, single-dose, 3-period, 3-treatment crossover study, 12 healthy adult volunteers were randomly assigned to treatment sequence. In each period, subjects received a single 40-mg dose of the assigned treatment (MPH ERCT chewed, MPH ERCT swallowed whole, or methylphenidate extended-release oral suspension [MEROS]). Blood samples for pharmacokinetic analysis were collected for 24 hours postdose. Key pharmacokinetic parameters included Cmax, AUC0-t, and AUC0-∞. FINDINGS: The geometric mean values for AUC0-t, AUC0-∞, and Cmax were similar for MPH ERCT chewed, MPH ERCT swallowed whole, and MEROS. In all pairwise between-treatment comparisons, the 90% CIs of the geometric mean ratios for AUC0-t, AUC0-∞, and Cmax were fully contained within the bioequivalence range of 80% to 125%. Early exposure over the first 4 hours after dosing (AUC0-4) was similar for MPH ERCT chewed versus swallowed whole; AUC0-4 was approximately 15% lower for MPH ERCT, either chewed or swallowed, compared with MEROS. Each treatment was generally well tolerated. IMPLICATIONS: There was no difference in overall rate or extent of exposure of methylphenidate when MPH ERCT was chewed versus swallowed whole by healthy volunteers.
Asunto(s)
Estimulantes del Sistema Nervioso Central/farmacocinética , Metilfenidato/farmacocinética , Administración Oral , Adulto , Área Bajo la Curva , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Disponibilidad Biológica , Estimulantes del Sistema Nervioso Central/administración & dosificación , Estudios Cruzados , Preparaciones de Acción Retardada/efectos adversos , Femenino , Humanos , Masculino , Masticación , Metilfenidato/administración & dosificación , Persona de Mediana Edad , Comprimidos , Equivalencia Terapéutica , Adulto JovenRESUMEN
We conducted an open-label, single-dose, randomized, crossover study in healthy adults to assess the impact of food on the bioavailability of 60 mg methylphenidate extended-release oral suspension (MEROS; Quillivant XR™)-a long-acting stimulant for the treatment of attention deficit hyperactivity disorder-by comparing the pharmacokinetic parameters under fed and fasting conditions. When MEROS 60 mg was administered under fed conditions compared with fasting conditions, the exposure of methylphenidate (d enantiomer) was higher, with a mean area under the plasma concentration-vs-time curve (AUC)0-t of 160.2 ng·h/mL vs 140.4 ng·h/mL, and a mean AUC0-inf of 163.2 ng·h/mL vs 143.7 ng·h/mL, respectively. The ratios of the ln-transformed geometric means for methylphenidate for AUC0-t and AUC0-inf were 119.5% (90%CI, 115.7% to 123.5%) and 119.0% (90%CI, 115.2% to 122.8%), respectively, within the standard 80% to 125% bioequivalence acceptance range indicating no food effect on the overall exposure (rate and extent). There was a small increase in the peak plasma concentration (127.6% [90%CI, 119.9% to 135.8%]). However, this effect was small and not likely to be clinically significant. Overall, MEROS 60 mg was safe in both the fed and fasting condition when administered to healthy volunteers in this study.
Asunto(s)
Ayuno/sangre , Metilfenidato/administración & dosificación , Metilfenidato/farmacocinética , Adulto , Anciano , Área Bajo la Curva , Disponibilidad Biológica , Estudios Cruzados , Preparaciones de Acción Retardada , Ingestión de Alimentos , Femenino , Interacciones Alimento-Droga , Humanos , Masculino , Persona de Mediana Edad , Embarazo , Distribución Aleatoria , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to determine the effect on family quality of life (QOL) of clonidine (CLON) and methylphenidate (MPH), used alone and in combination, in treating attention-deficit/hyperactivity disorder (ADHD). METHODS: Two proxy QOL measures were used in a multicenter, double-blind, placebo-controlled 16-week trial of 122 children, ages 7-12 years, with ADHD. Children were randomized to one of four groups in which they received MPH, CLON, a combination of drugs, or placebo. QOL was measured with the Daily Hassles Scale and the Impact on Family Scale at baseline and at 16 weeks. RESULTS: In a general linear model repeated measures analysis, treatment groups improved over a 16-week period compared to placebo for Daily Hassles and Impact on Family, as well as in symptoms measured by the ADHD Rating Scale. QOL measures correlated moderately with efficacy and symptom measures. CONCLUSION: This study provides evidence that measures of QOL for the family are sensitive to pharmacological treatment of ADHD. The correlation pattern of the QOL measures with symptom and efficacy variables supported family QOL as a related but separate construct. Clonidine for Attention-Deficit/Hyperactivity Disorder Treatment Study (CAT) Trial Registry Name: Clinicaltrials.gov; ID Number, NCT00031395; URL, http://clinicaltrials.gov/ct/show/NCT00031395?order=8/ .
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Clonidina/uso terapéutico , Metilfenidato/uso terapéutico , Agonistas alfa-Adrenérgicos/uso terapéutico , Niño , Método Doble Ciego , Quimioterapia Combinada , Salud de la Familia , Femenino , Humanos , Modelos Lineales , Masculino , Escalas de Valoración Psiquiátrica , Calidad de VidaRESUMEN
OBJECTIVE: To determine the efficacy and safety of clonidine, used alone or in combination with methylphenidate, in treating attention-deficit/hyperactivity disorder (ADHD). METHOD: A 16-week, randomized, double-blind, placebo-controlled clinical trial was conducted in 122 children, ages 7 to 12, with any subtype of ADHD, randomly assigned to clonidine, methylphenidate, clonidine in combination with methylphenidate, or placebo according to a 2 x 2 factorial design. In two successive 4-week titration periods, clonidine (or matching placebo) and added methylphenidate (or matching placebo) were adjusted to optimal doses and then continued for 8 weeks. The primary efficacy outcome was changed from baseline to week 16 on the Conners Teachers Abbreviated Symptom Questionnaire. Secondary outcomes included the Conners Abbreviated Symptom Questionnaire for Parents and the Children's Global Assessment Scale. RESULTS: On the Conners Teachers Abbreviated Symptom Questionnaire, clonidine was not found to improve ADHD symptoms, whereas subjects treated with methylphenidate showed significant improvement compared to those not treated with methylphenidate. Subjects treated with clonidine had greater improvements on the Conners Abbreviated Symptom Questionnaire for Parents and Children's Global Assessment Scale, but also a higher rate of sedation compared with subjects not treated with clonidine. CONCLUSIONS: Based on the Conners Teachers Abbreviated Symptom Questionnaire, methylphenidate offers the best combination of efficacy and tolerability for ADHD. Clonidine was well tolerated despite the frequency of sedation and did offer some benefit.
Asunto(s)
Agonistas alfa-Adrenérgicos/uso terapéutico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Clonidina/uso terapéutico , Agonistas alfa-Adrenérgicos/efectos adversos , Estimulantes del Sistema Nervioso Central/efectos adversos , Estimulantes del Sistema Nervioso Central/uso terapéutico , Niño , Clonidina/efectos adversos , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Metilfenidato/efectos adversos , Metilfenidato/uso terapéutico , Determinación de la Personalidad , Medio Social , Resultado del TratamientoRESUMEN
OBJECTIVE: To measure the primary and secondary school-age neurologic, cognitive, and educational outcomes in a cohort of extremely premature infants born after the introduction of exogenous surfactant therapy in a circumscribed region. METHODS: Two hundred thirteen infants born at <29 weeks' gestation were cared for at a regional referral center during 1985-1987. At primary school age, neurologic and cognitive outcomes, educational achievement, school placement, health status, and socioeconomic status were determined by follow-up visit. At secondary school age, school placement and health status were evaluated by telephone interview. RESULTS: One hundred thirty-two infants survived to school age, of whom 127 (96%) were evaluated in 1992-1995 and 126 (95%) were evaluated in 2000. Mean ages were 7.0 years at first follow-up and 14.1 years at second follow-up. At primary-school age follow-up, 19 children (15%) had cerebral palsy, 24 (19%) had a general cognitive index <70, and 41 (32%) were placed in a self-contained, special classroom. Thirty-nine children (31%) had no physical or educational impairment, whereas 27 (21%) had at least 1 severe disability. At secondary school age, cerebral palsy incidence remained unchanged, whereas 36 children (29%) were placed in a special classroom. Fifty-one children (41%) had no physical or educational impairment, whereas 24 (19%) had at least 1 severe disability. Neonatal intraventricular hemorrhage and low socioeconomic status were the strongest predictors of adverse outcomes. CONCLUSIONS: Premature infants born in the surfactant era remain at high risk of neurodevelopmental compromise. Although many of these children do well, a significant minority will require intensive special educational services through secondary school age.