Mirochnick M, Cooper E, McIntosh K, Xu J, Lindsey J, Jacobus D, Mofenson L, Sullivan J L, Dankner W, Frenkel L M, Nachman S, Wara D W, Johnson D, Bonagura V R, Rathore M H, Cunningham C K, McNamara J
Boston Medical Center, Boston, Massachusetts, USA.
Antimicrob Agents Chemother. 1999 Nov;43(11):2586-91. doi: 10.1128/AAC.43.11.2586.
Although dapsone is a commonly used alternative agent for prophylaxis against Pneumocystis carinii pneumonia in children intolerant to trimethoprim-sulfamethoxazole, there are few data that describe dapsone pharmacokinetics in children. We studied dapsone pharmacokinetics in 30 children (median age, 2.8 years; age range, 0. 3 to 12 years) receiving a new proprietary liquid preparation by three dosing regimens (1 mg/kg of body weight daily, 2 mg/kg daily, or 4 mg/kg weekly). Dosing of children with 2 mg/kg daily or 4 mg/kg weekly resulted in peak concentrations equivalent to those reached in adults receiving 100-mg tablets daily. For the entire population, the median half-life was 22.2 h (range, 7.1 to 40.3 h), the median oral clearance was 0.0365 liter/kg/h (range, 0.0104 to 0.1021 liter/kg/h), and the median oral apparent volume of distribution was 1.13 liters/kg (range, 0.50 to 2.32 liters/kg). The median dapsone oral clearance was significantly increased in those infants less than 2 years of age compared to the oral clearance in those over 2 years of age (0.0484 versus 0.0278 liter/kg/h; P = 0.011). These data suggest that absorption of this liquid preparation is adequate and that the concentrations in the sera of children receiving 2 mg/kg daily or 4 mg/kg weekly are equivalent to those seen in adults receiving standard dapsone dosing. Dapsone oral clearance appears to be increased in children under 2 years of age.
虽然氨苯砜是用于对不耐受甲氧苄啶 - 磺胺甲恶唑的儿童预防卡氏肺孢子虫肺炎的常用替代药物,但描述氨苯砜在儿童体内药代动力学的数据很少。我们研究了30名儿童(中位年龄2.8岁;年龄范围0.3至12岁)接受一种新的专利液体制剂的三种给药方案(每日1 mg/kg体重、每日2 mg/kg或每周4 mg/kg)后的氨苯砜药代动力学。每日给予2 mg/kg或每周给予4 mg/kg的儿童给药后达到的峰值浓度与接受每日100 mg片剂的成人所达到的峰值浓度相当。对于整个研究人群,中位半衰期为22.2小时(范围7.1至40.3小时),中位口服清除率为0.0365升/千克/小时(范围0.0104至0.1021升/千克/小时),中位口服表观分布容积为1.13升/千克(范围0.50至2.32升/千克)。与2岁以上儿童的口服清除率相比,2岁以下婴儿的氨苯砜中位口服清除率显著增加(0.0484对0.0278升/千克/小时;P = 0.011)。这些数据表明这种液体制剂的吸收是充分的,并且接受每日2 mg/kg或每周4 mg/kg的儿童血清中的浓度与接受标准氨苯砜给药的成人中所见浓度相当。2岁以下儿童的氨苯砜口服清除率似乎有所增加。