ArticleEuropean journal of clinical pharmacology2011
Population pharmacokinetic modeling of tramadol and its O-desmethyl metabolite in plasma and breast milk.
Article in European journal of clinical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 39 citations in OpenAlex.
- Pharmacokinetics of Transfer of Azithromycin into the Breast Milk of African Mothers.Antimicrobial agents and chemotherapy · 2015Trial
- Methodologies for Population Pharmacokinetic Modeling of Target-Site Drug Exposure: A Narrative Review of Current Strategies.Clinical pharmacokinetics · 2026Review
- Role of Pharmacogenetics on Tramadol Pharmacokinetics: A Population Pharmacokinetic Model.European journal of drug metabolism and pharmacokinetics · 2026Article
- Clinical study design and modeling approaches to study secretion of drugs in human milk.Frontiers in pediatrics · 2026Review
- Population Pharmacokinetics and Transfer of Gabapentin When Used as a Pain Adjunct for Cesarean Deliveries.CPT: pharmacometrics & systems pharmacology · 2025Observational
- The MILK study: Investigating intergenerational transmission of low-calorie sweeteners in breast milk.Contemporary clinical trials communications · 2023Article
- Population Pharmacokinetic Model for Tramadol and O-desmethyltramadol in Older Patients.European journal of drug metabolism and pharmacokinetics · 2022Article
- Evaluation of the estimation and classification performance of NONMEM when applying mixture model for drug clearance.CPT: pharmacometrics & systems pharmacology · 2021Article
- Neonatal Exposure to Tramadol through Mother's Breast Milk.Journal of analytical toxicology · 2021Article
- Evaluation of the Effect of CYP2D6 Genotypes on Tramadol andPharmaceutics · 2019Article
- Population pharmacokinetic analysis of tramadol andDrug design, development and therapy · 2019Article
- Drugs in Lactation.Pharmaceutical research · 2018Review
- Analgesic Activity of Tramadol and Buprenorphine after Voluntary Ingestion by Rats (Rattus norvegicus).Journal of the American Association for Laboratory Animal Science : JAALAS · 2016Article
- Pharmacokinetics of piperaquine transfer into the breast milk of Melanesian mothers.Antimicrobial agents and chemotherapy · 2015Article
- Population PK modelling and simulation based on fluoxetine and norfluoxetine concentrations in milk: a milk concentration-based prediction model.British journal of clinical pharmacology · 2014Article
- Mathematical model approach to describe tumour response in mice after vaccine administration and its applicability to immune-stimulatory cytokine-based strategies.The AAPS journal · 2013Article
- Pharmacogenomic considerations in opioid analgesia.Pharmacogenomics and personalized medicine · 2012Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe aim of this investigation was to demonstrate that nonlinear mixed-effects population pharmacokinetic (PK) modeling can be used to evaluate data from studies of drug transport/excretion into human milk and hence to estimate infant exposure.
methodsA sparse dataset from a previously published study of the use of oral tramadol for post-cesarean pain management in 75 lactating women was used. Milk and plasma samples were collected during days 2-4 of lactation, and tramadol and O-desmethyltramadol (ODT) concentration measurements in these samples were available. Absolute infant dose was obtained from the concentration measurements and estimated milk volume ingested, and expressed in micrograms per kilogram per day. Relative infant dose was calculated as a percentage of the absolute infant dose divided by the maternal dose (μg/kg/day). Nonlinear mixed-effects modeling was used to fit a population PK model to the data.
resultsThe disposition of tramadol and ODT in plasma and the transition of these substances into milk were characterized by a five-compartment population PK mixture model with first-order absorption. The polymorphic ODT formation clearance in the plasma compartment was able to be characterized in both CYP2D6-poor and -extensive metabolizers. Milk creamatocrit was a significant covariate in ODT transfer between the plasma and milk compartments. The estimated relative infant doses in extensive and poor metabolizers, respectively, were 2.16 ± 0.57 and 2.60 ± 0.57% for tramadol, and 0.93 ± .20 and 0.47 ± 0.10% for ODT.
conclusionsThis study demonstrates that a population PK approach with sparse sampling of analytes in milk and plasma can yield quality information about the transfer process and that it also can be used to estimate the extent of infant exposure to maternal drugs via milk.
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