Persistence of nevirapine in breast milk and plasma of mothers and their children after single-dose administration
| العنوان: | Persistence of nevirapine in breast milk and plasma of mothers and their children after single-dose administration |
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| المؤلفون: | Rose Kabasinguzi, Michael Kurowski, Andrea Kunz, Charlotte Kloft, Kizito Mugenyi, Monika Frank, Gundel Harms, Astrid Weidenhammer |
| المصدر: | Journal of Antimicrobial Chemotherapy. 63:170-177 |
| بيانات النشر: | Oxford University Press (OUP), 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Adult, Male, Microbiology (medical), Nevirapine, Population, Mothers, Physiology, HIV Infections, Breast milk, Plasma, Pharmacokinetics, Tandem Mass Spectrometry, Lactation, medicine, Humans, Uganda, Pharmacology (medical), education, Pharmacology, education.field_of_study, Milk, Human, Reverse-transcriptase inhibitor, business.industry, Infant, Newborn, Infectious Disease Transmission, Vertical, Infectious Diseases, medicine.anatomical_structure, Immunology, Female, Pregnant Women, business, Breast feeding, Postpartum period, Chromatography, Liquid, medicine.drug |
| الوصف: | OBJECTIVES: Nevirapine is widely used in the developing world for the prevention of mother-to-child transmission (PMTCT) of HIV. A single mutation in the HIV genome is sufficient to lead to significant nevirapine resistance. Persistence of low-level drug concentrations in body compartments can foster resistance formation. In this study concentration-time courses of nevirapine after single-dose administration were analysed over an extended post-partum period. PATIENTS AND METHODS: Breast milk and plasma samples of 62 HIV-positive Ugandan mother-child pairs who had received single-dose nevirapine were collected at delivery and 1 2 and 6 weeks post-partum. Nevirapine concentrations were quantified by LC/tandem-mass-spectrometry using a quantification limit of 15 ng/mL and a population pharmacokinetic (PK) analysis was performed. RESULTS: Concentration-time profiles in breast milk maternal plasma and child plasma showed similar shapes. At week 1 median nevirapine concentrations were 164 ng/mL in maternal plasma 114 ng/mL in breast milk and 183 ng/mL in child plasma. The population PK model predicted nevirapine concentrations>10 ng/mL (IC50 for nevirapine) for 13 days in breast milk 14 days in maternal plasma and 18 days in child plasma in 80% of the samples. CONCLUSIONS: Nevirapine concentrations were present for 2-3 weeks in the three compartments. The concentrations are probably sufficiently high to protect most breastfed children from HIV transmission during the first 2 weeks. The long presence of slowly decreasing levels of nevirapine is likely to induce resistance formation. Post-natal addition of antiretrovirals for 1 week only as recommended in the current PMTCT guidelines will not suffice to avoid nevirapine resistance formation. |
| تدمد: | 1460-2091 0305-7453 |
| DOI: | 10.1093/jac/dkn441 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ced294bd86b489793ba4f9fa43733ce9 https://doi.org/10.1093/jac/dkn441 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ced294bd86b489793ba4f9fa43733ce9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602091 03057453 |
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| DOI: | 10.1093/jac/dkn441 |