Geographical Variability in Paromomycin Pharmacokinetics Does Not Explain Efficacy Differences between Eastern African and Indian Visceral Leishmaniasis Patients
| العنوان: | Geographical Variability in Paromomycin Pharmacokinetics Does Not Explain Efficacy Differences between Eastern African and Indian Visceral Leishmaniasis Patients |
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| المؤلفون: | Thomas P. C. Dorlo, Jaya Chakravarty, Eltahir A G Khalil, Ahmed Eleojo Musa, Yalemtsehay Mekonnen, Madhukar Rai, Luka Verrest, Rashid Aman, Zewdu Hurissa, Workagegnehu Hailu, Samson Tesfaye, Jos H. Beijnen, Monique Wasunna, Gilbert Kokwaro, Smita Kshirsagar, Asrat Hailu, Mahmoud Mudawi, Eyasu Makonnen, Alwin D. R. Huitema, Fabiana Alves, Brima M. Younis, Shyam Sundar |
| المصدر: | Clinical Pharmacokinetics |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, Paromomycin, Sodium stibogluconate, 030231 tropical medicine, 030106 microbiology, Population, Antiprotozoal Agents, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Interquartile range, Internal medicine, parasitic diseases, medicine, Humans, Pharmacology (medical), Original Research Article, education, Pharmacology, education.field_of_study, business.industry, medicine.disease, Kenya, Bioavailability, Regimen, Visceral leishmaniasis, Antimony Sodium Gluconate, Leishmaniasis, Visceral, business, medicine.drug |
| الوصف: | Introduction Intramuscular paromomycin monotherapy to treat visceral leishmaniasis (VL) has been shown to be effective for Indian patients, while a similar regimen resulted in lower efficacy in Eastern Africa, which could be related to differences in paromomycin pharmacokinetics. Methods Pharmacokinetic data were available from two randomized controlled trials in VL patients from Eastern Africa and India. African patients received intramuscular paromomycin monotherapy (20 mg/kg for 21 days) or combination therapy (15 mg/kg for 17 days) with sodium stibogluconate. Indian patients received paromomycin monotherapy (15 mg/kg for 21 days). A population pharmacokinetic model was developed for paromomycin in Eastern African and Indian VL patients. Results Seventy-four African patients (388 observations) and 528 Indian patients (1321 observations) were included in this pharmacokinetic analysis. A one-compartment model with first-order kinetics of absorption and elimination best described paromomycin in plasma. Bioavailability (relative standard error) was 1.17 (5.18%) times higher in Kenyan and Sudanese patients, and 2.46 (24.5%) times higher in Ethiopian patients, compared with Indian patients. Ethiopian patients had an approximately fourfold slower absorption rate constant of 0.446 h–1 (18.2%). Area under the plasma concentration-time curve for 24 h at steady-state (AUCτ,SS) for 15 mg/kg/day (median [interquartile range]) was higher in Kenya and Sudan (172.7 µg·h/mL [145.9–214.3]) and Ethiopia (230.1 µg·h/mL [146.3–591.2]) compared with India (97.26 µg·h/mL [80.83–123.4]). Conclusion The developed model provides detailed insight into the pharmacokinetic differences among Eastern African countries and India, however the resulting differences in paromomycin exposure do not seem to explain the geographical differences in paromomycin efficacy in the treatment of VL patients. Supplementary Information The online version contains supplementary material available at 10.1007/s40262-021-01036-8. |
| تدمد: | 1179-1926 0312-5963 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f3f64d996bde4fb2285008bb1aa80e38Test https://doi.org/10.1007/s40262-021-01036-8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f3f64d996bde4fb2285008bb1aa80e38 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 11791926 03125963 |
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