{"doi":"10.3389/fmolb.2023.1130206","title":"Hydroxyurea pharmacokinetics and precision dosing in low-resource settings","abstract":"Introduction: Hydroxyurea is effective disease-modifying treatment for sickle cell anemia (SCA). Escalation to maximum tolerated dose (MTD) achieves superior benefits without additional toxicities, but requires dose adjustments with serial monitoring. Pharmacokinetic (PK)-guided dosing can predict a personalized optimal dose, which approximates MTD and requires fewer clinical visits, laboratory assessments, and dose adjustments. However, PK-guided dosing requires complex analytical techniques unavailable in low-resource settings. Simplified hydroxyurea PK analysis could optimize dosing and increase access to treatment. Methods: Concentrated stock solutions of reagents for chemical detection of serum hydroxyurea using HPLC were prepared and stored at −80C. On the day of analysis, hydroxyurea was serially diluted in human serum, then spiked with N-methylurea as an internal standard and analyzed using two commercial HPLC machines: 1) standard benchtop Agilent with 449 nm detector and 5 micron C18 column; and 2) portable PolyLC with 415 nm detector and 3.5 micron C18 column. After validation in the United States, the portable HPLC and chemicals were transported to Tanzania. Results: A calibration curve using hydroxyurea 2-fold dilutions ranging from 0 to 1000 µM was plotted against the hydroxyurea:N-methylurea ratio. In the United States, both HPLC systems yielded calibration curves with R 2 > 0.99. Hydroxyurea prepared at known concentrations confirmed accuracy and precision within 10%–20% of the actual values. Both HPLC systems measured hydroxyurea with <10% variance from the prepared concentrations, and paired analysis of samples on both machines documented <15% variance. Serial measurements of 300 and 100 μM concentrations using the PolyLC system were precise with 2.5% coefficient of variance. After transport to Tanzania with setup and training, the modified PolyLC HPLC system produced similar calibration curves with R 2 > 0.99. Conclusion: Increasing access to hydroxyurea for people with SCA requires an approach that eases financial and logistical barriers while optimizing safety and benefits, especially in low-resource settings. We successfully modified a portable HPLC instrument to quantify hydroxyurea, validated its precision and accuracy, and confirmed capacity building and knowledge transfer to Tanzania. HPLC measurement of serum hydroxyurea is now feasible in low-resource settings using available laboratory infrastructure. PK-guided dosing of hydroxyurea will be tested prospectively to achieve optimal treatment responses.","journal":"Frontiers in Molecular Biosciences","year":2023,"id":365601,"datarank":0.3282233049223355,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.03633678256403843,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.03633678256403843,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":3,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9565,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1078679,"name":"Mwesige Charles","orcid":"0000-0001-9330-6487","position":1,"is_corresponding":false},{"id":1121892,"name":"Kathryn McElhinney","orcid":null,"position":2,"is_corresponding":false},{"id":307301,"name":"Min Dong","orcid":"0000-0002-8552-8298","position":3,"is_corresponding":false},{"id":1097585,"name":"Alexandra Power‐Hays","orcid":"0000-0002-5823-0218","position":4,"is_corresponding":false},{"id":1121460,"name":"Thad A. Howard","orcid":"0000-0002-9257-6343","position":5,"is_corresponding":false},{"id":295601,"name":"Alexander A. Vinks","orcid":"0000-0003-4224-2967","position":6,"is_corresponding":false},{"id":310459,"name":"Emmanuela E. Ambrose","orcid":"0000-0001-6225-6448","position":7,"is_corresponding":false},{"id":310457,"name":"Russell E. Ware","orcid":"0000-0001-9582-0594","position":8,"is_corresponding":false},{"id":781596,"name":"Luke R. Smart","orcid":"0000-0003-4083-0060","position":0,"is_corresponding":true}],"reference_count":19,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:14:50.885797Z","pmid":"37325474","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}