BACKGROUND AND OBJECTIVES The dosing of cycloserine and terizidone is the same, as both drugs are considered equivalent or used interchangeably. Nevertheless, it is not certain from the literature that these drugs are interchangeable. Therefore, the amount of cycloserine resulting from the metabolism of terizidone and the relationship with hepatic function were determined. METHODS This prospective clinical study involved 39 patients with drug-resistant tuberculosis admitted for an intensive phase of treatment. Cycloserine pharmacokinetic parameters for individual patients, like area under the curve (AUC), clearance (CLm/F), peak concentration (Cmax) and trough concentration (Cmin), were calculated from a previously validated joint population pharmacokinetic model of terizidone and cycloserine. Correlation and regression analyses were performed for pharmacokinetic parameters and unconjugated bilirubin (UB), conjugated bilirubin (CB), albumin, the ratio of aspartate transaminase to alanine aminotransferase (AST/ALT), or binding affinity of UB to albumin (Kaf), using R statistical software version 3.5.3. RESULTS Thirty-eight patients took a daily dose of 750 mg terizidone, while one took 500 mg. The amount of cycloserine [median (range)] that emanated from terizidone metabolism was 51.6 (0.64-374) mg. Cmax (R2 = 22%, p = 0.003) and Cmin (R2 = 10.6%, p = 0.044) were significantly associated with increased CB concentration. Cmax was significantly associated with increased Kaf (R2 = 10.1%, p = 0.048), while high CLm/F was significantly associated with decreased AST/ALT (R2 = 21%, p = 0.003). CONCLUSIONS Cycloserine is not interchangeable with terizidone, as amounts are lower than expected. Cycloserine may be a predisposing factor to the development of hyperbilirubinaemia, as CLm/F is affected by hepatic function.

中文翻译：

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耐药性肺结核患者中特立西酮代谢产生的环丙沙星的含量及其与肝功能的关系。

背景与目的环丝氨酸和terizidone的剂量相同，因为这两种药物被认为是等效的或可互换使用。然而，从文献中不能确定这些药物是可互换的。因此，确定了由特立齐酮代谢产生的环丝氨酸的量以及与肝功能的关系。方法这项前瞻性临床研究纳入了接受强化治疗的39例耐药结核患者。根据预先验证的特立西酮和环丝氨酸的联合人群药代动力学模型计算出个别患者的环氯碱的药代动力学参数，如曲线下面积（AUC），清除率（CLm / F），峰浓度（Cmax）和谷浓度（Cmin）。使用药代动力学参数和未结合胆红素（UB），结合胆红素（CB），白蛋白，天冬氨酸转氨酶与丙氨酸氨基转移酶的比率（AST / ALT）或UB与白蛋白的结合亲和力（Kaf）进行相关和回归分析R统计软件版本3.5.3。结果38例患者每日服用750 mg特立西酮，而1例患者每日服用500 mg。特立齐酮代谢产生的环丝氨酸[中位数（范围）]为51.6（0.64-374）mg。Cmax（R2 = 22％，p = 0.003）和Cmin（R2 = 10.6％，p = 0.044）与CB浓度升高显着相关。Cmax与Kaf升高显着相关（R2 = 10.1％，p = 0.048），而高CLm / F与AST / ALT降低显着相关（R2 = 21％，p = 0.003）。结论Cyclorine与Terizidone不可互换，因为其含量低于预期。Cyclorine可能是高胆红素血症发展的诱因，因为CLm / F受肝功能影响。