Department of Paediatrics and Child Health and Tygerberg Children's Hospital, Faculty of Health Sciences, Stellenbosch University, South Africa.
Tuberculosis (Edinb). 2011 May;91(3):196-207. doi: 10.1016/j.tube.2011.02.004. Epub 2011 Mar 22.
The dosages of antituberculosis agents recommended for treatment of childhood tuberculosis often reflect those for adult patients with similar mg/kg body weight dosages and ranges advised. Literature relating to the pharmacokinetics and pharmacodynamics of rifampicin (RMP) is reviewed and the serum concentrations reached by adults, both patients and healthy volunteers and children, established or not established on RMP, compared. Straight line regression of maximum RMP serum concentrations (C(max)) on dosage, weighted for the number of individuals, found slopes (SE) of 1.025 (0.067) and 0.881 (0.046) respectively for adult volunteers not established and established on RMP (P = 0.076), and similarly 0.748 (0.057) and 0.684 (0.038) respectively for adult patients (P < 0.001) and 0.622 (0.050) and 0.368 (0.041) respectively for children (P < 0.001). These results indicate that for equivalent RMP dosages adult patients reach a lower C(max) than adult volunteers and that adults, both volunteers and patients established on RMP reach higher C(max) values than children; children established on RMP require approximately twice the mg/kg body weight dosage of RMP to reach serum concentrations equivalent to those of adults. It is noteworthy that many adult patients receiving currently recommended RMP dosages also do not reach the often recommended RMP 2 h serum concentration of 8 μg/mL.
推荐用于治疗儿童结核病的抗结核药物剂量通常反映了类似 mg/kg 体重剂量范围的成人患者的剂量。本文回顾了利福平(RMP)的药代动力学和药效学文献,并比较了成人患者(包括接受和未接受 RMP 治疗的患者)和儿童志愿者(包括接受和未接受 RMP 治疗的儿童)的血清浓度。对未接受 RMP 治疗和接受 RMP 治疗的成人志愿者的最大 RMP 血清浓度(C(max))与剂量进行直线回归,加权个体数量,斜率(SE)分别为 1.025(0.067)和 0.881(0.046)(P = 0.076),同样对于成人患者(P < 0.001)分别为 0.748(0.057)和 0.684(0.038),对于儿童(P < 0.001)分别为 0.622(0.050)和 0.368(0.041)。这些结果表明,对于等效的 RMP 剂量,成年患者达到的 C(max)低于成年志愿者,并且接受 RMP 治疗的成年患者和志愿者达到的 C(max)值高于儿童;接受 RMP 治疗的儿童需要大约两倍的 RMP 剂量/kg 体重才能达到与成人相当的血清浓度。值得注意的是,许多接受目前推荐的 RMP 剂量的成年患者也未达到通常推荐的 RMP 2 h 血清浓度 8 μg/mL。