Treatment regimens for post-kala-azar dermal leishmaniasis (PKDL) are usually extrapolated from those for visceral leishmaniasis (VL), but drug pharmacokinetics (PK) can differ due to disease-specific variations in absorption, distribution, and elimination. This study characterized PK differences in paromomycin and miltefosine between 109 PKDL and 264 VL patients from Eastern Africa. VL patients showed 0.55-fold (95% confidence interval [CI], .41–.74) lower capacity for paromomycin saturable reabsorption in renal tubules, and required a 1.44-fold (95% CI, 1.23–1.71) adjustment when relating renal clearance to creatinine-based estimated glomerular filtration rate. Miltefosine bioavailability in VL patients was lowered by 69% (95% CI, 62%–76%) at treatment start. Comparing PKDL to VL patients on the same regimen, paromomycin plasma exposures were 0.74- to 0.87-fold, while miltefosine exposure until the end of treatment day was 1.4-fold. These pronounced PK differences between PKDL and VL patients in Eastern Africa highlight the challenges of directly extrapolating dosing regimens from one leishmaniasis presentation to another.

中文翻译：

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东非 Kala-Azar 后皮肤利什曼病患者和内脏利什曼病患者巴龙霉素和米替福新药代动力学的疾病特异性差异


黑热病后皮肤利什曼病 （PKDL） 的治疗方案通常从内脏利什曼病 （VL） 的治疗方案推断而来，但由于吸收、分布和消除的疾病特异性变化，药物药代动力学 （PK） 可能有所不同。本研究表征了来自东非的 109 例 PKDL 和 264 例 VL 患者在巴龙霉素和米替福新方面的 PK 差异。VL 患者肾小管中巴龙霉素可饱和重吸收的能力降低了 0.55 倍 （95% 置信区间 [CI]，.41-.74），当将肾清除率与基于肌酐的估计肾小球滤过率相关联时，需要调整 1.44 倍 （95% CI，1.23-1.71）。治疗开始时，VL 患者的 miltefosine 生物利用度降低了 69% （95% CI，62%–76%）。将 PKDL 与相同方案的 VL 患者进行比较，巴龙霉素血浆暴露量为 0.74 至 0.87 倍，而米替福新暴露至治疗日结束为 1.4 倍。东非 PKDL 和 VL 患者之间的这些显着 PK 差异凸显了将给药方案从一种利什曼病表现直接外推到另一种表现的挑战。