van der Laan Louvina E, Garcia-Prats Anthony J, Schaaf H Simon, Winckler Jana L, Draper Heather, Norman Jennifer, Wiesner Lubbe, McIlleron Helen, Denti Paolo, Hesseling Anneke C
Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Department of Medicine, Division of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa.
Front Pharmacol. 2021 Oct 8;12:722204. doi: 10.3389/fphar.2021.722204. eCollection 2021.
Given the high prevalence of multidrug-resistant (MDR)-TB in high HIV burden settings, it is important to identify potential drug-drug interactions between MDR-TB treatment and widely used nucleoside reverse transcriptase inhibitors (NRTIs) in HIV-positive children. Population pharmacokinetic models were developed for lamivudine (n = 54) and abacavir (n = 50) in 54 HIV-positive children established on NRTIs; 27 with MDR-TB (combinations of high-dose isoniazid, pyrazinamide, ethambutol, ethionamide, terizidone, fluoroquinolones, and amikacin), and 27 controls without TB. Two-compartment models with first-order elimination and transit compartment absorption described both lamivudine and abacavir pharmacokinetics, respectively. Allometric scaling with body weight adjusted for the effect of body size. Clearance was predicted to reach half its mature value 2 (lamivudine) and 3 (abacavir) months after birth, with completion of maturation for both drugs at 2 years. No significant difference was found in key pharmacokinetic parameters of lamivudine and abacavir when co-administered with routine drugs used for MDR-TB in HIV-positive children.
鉴于在艾滋病毒高负担环境中耐多药结核病（MDR-TB）的高流行率，识别艾滋病毒阳性儿童中MDR-TB治疗与广泛使用的核苷类逆转录酶抑制剂（NRTIs）之间潜在的药物相互作用非常重要。针对54名接受NRTIs治疗的艾滋病毒阳性儿童建立了拉米夫定（n = 54）和阿巴卡韦（n = 50）的群体药代动力学模型；其中27名患有MDR-TB（高剂量异烟肼、吡嗪酰胺、乙胺丁醇、乙硫异烟胺、特立齐酮、氟喹诺酮类和阿米卡星的组合），27名无结核病的对照儿童。具有一级消除和转运室吸收的二室模型分别描述了拉米夫定和阿巴卡韦的药代动力学。通过体重进行异速缩放以调整体型的影响。预计清除率在出生后2个月（拉米夫定）和3个月（阿巴卡韦）达到其成熟值的一半，两种药物均在2岁时完成成熟。在艾滋病毒阳性儿童中，拉米夫定和阿巴卡韦与用于MDR-TB的常规药物合用时，关键药代动力学参数未发现显著差异。
