妊娠合并与弓形虫眼病患者比较的磺胺嘧啶血浆浓度：一项病例对照研究。

Sulfadiazine plasma concentrations in women with pregnancy-acquired compared to ocular toxoplasmosis under pyrimethamine and sulfadiazine therapy: a case-control study.

机构信息

Institute of Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Bonn, Germany.

Laborärzte Sindelfingen, Sindelfingen, Germany.

出版信息

Eur J Med Res. 2020 Nov 23;25(1):59. doi: 10.1186/s40001-020-00458-7.

DOI:10.1186/s40001-020-00458-7

PMID:33228795

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7686675/

Abstract

BACKGROUND

Dosing recommendations for the treatment of pregnancy-acquired toxoplasmosis are empirical and widely based on experimental data. There are no pharmacological data on pregnant women with acute Toxoplasma gondii infection under treatment with pyrimethamine (PY) and sulfadiazine (SA) and our study intends to tighten this gap.

METHODS

In this retrospective case-control study, we included 89 pregnant women with primary Toxoplasma infection (PT) treated with PY (50 mg first dose, then 25 mg/day), SA (50 mg/kg of body weight/day), and folinic acid (10-15 mg per week). These were compared to a group of 17 women with acute ocular toxoplasmosis (OT) treated with an initial PY dose of 75 mg, thereafter 25 mg twice a day but on the same SA and folinic acid regimen. The exact interval between drug intake and blood sampling and co-medication had not been recorded. Plasma levels of PY and SA were determined 14 ± 4 days after treatment initiation using liquid chromatography-mass spectrometry and compared using the Mann-Whitney U test at a p < 0.05 level.

RESULTS

In 23 PT patients (26%), SA levels were below 20 mg/l. Fifteen of these 23 patients (17% of all patients) in parallel presented with PY levels below 700 µg/l. Both drug concentrations differed remarkably between individuals and groups (PY: PT median 810 µg/l, 95% CI for the median [745; 917] vs. OT 1230 µg/l [780; 1890], p = 0.006; SA: PT 46.2 mg/l [39.9; 54.4] vs. OT 70.4 mg/l [52.4; 89], p = 0.015) despite an identical SA dosing scheme.

CONCLUSIONS

SA plasma concentrations were found in the median 34% lower in pregnant women with PT compared to OT patients and fell below a lower reference value of 50 mg/l in a substantial portion of PT patients. The interindividual variability of plasma concentrations in combination with systematically lower drug levels and possibly a lower compliance in pregnant women may thus account for a still not yet supportable transmission risk. Systematic drug-level testing in PT under PY/SA treatment deserves to be considered.

摘要

背景

治疗妊娠获得性弓形体病的剂量建议是经验性的，并且广泛基于实验数据。目前尚无关于接受乙嘧啶（PY）和磺胺嘧啶（SA）治疗的急性刚地弓形虫感染孕妇的药理学数据，我们的研究旨在填补这一空白。

方法

在这项回顾性病例对照研究中，我们纳入了 89 名初次感染弓形体（PT）的孕妇，她们接受了 PY（首剂 50mg，然后每天 25mg）、SA（50mg/kg 体重/天）和叶酸治疗。这些患者与 17 名患有急性眼部弓形体病（OT）的女性进行了比较，后者接受了初始剂量为 75mg 的 PY 治疗，此后每天两次 25mg，但采用相同的 SA 和叶酸方案。药物摄入和采血之间的精确间隔以及合并用药均未记录。采用液相色谱-质谱法在治疗开始后 14±4 天测定血浆中 PY 和 SA 的水平，并使用 Mann-Whitney U 检验在 p<0.05 水平上进行比较。

结果

在 23 名 PT 患者（26%）中，SA 水平低于 20mg/L。其中 15 名患者（所有患者的 17%）同时出现 PY 水平低于 700µg/L。两种药物浓度在个体和组间差异显著（PY：PT 中位数 810µg/L，95%CI 中位数 [745；917] 与 OT 中位数 1230µg/L [780；1890]，p=0.006；SA：PT 中位数 46.2mg/L [39.9；54.4] 与 OT 中位数 70.4mg/L [52.4；89]，p=0.015），尽管 SA 给药方案相同。

结论

与 OT 患者相比，PT 孕妇的 SA 血浆浓度中位数低 34%，且相当一部分 PT 患者的 SA 血浆浓度低于 50mg/L 的下限参考值。个体间血浆浓度的变异性，再加上药物水平较低，以及孕妇可能的低依从性，可能导致仍然无法支持的传播风险。在接受 PY/SA 治疗的 PT 患者中，系统的药物水平检测值得考虑。