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Both toxicity and cross-resistance, commonly seen for other aminoglycosides, appear relatively low owing to its distinct chemical structure.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To perform a population pharmacokinetic (PPK) analysis and predict an efficacious dose based on data from a first-in-human Phase I trial.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The drug was administered intravenously over 30\u2005min in five ascending-dose groups ranging from 0.3 to 30\u2005mg\/kg. Plasma and urine samples were collected from 30 healthy volunteers. PPK model development was performed stepwise and the final model was used for PTA analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A mammillary four-compartment PPK model, with linear elimination and a renal fractional excretion of 90%, described the data. Apramycin clearance was proportional to the absolute estimated glomerular filtration rate (eGFR). All fixed effect parameters were allometrically scaled to total body weight (TBW). Clearance and steady-state volume of distribution were estimated to 5.5\u2005L\/h and 16\u2005L, respectively, for a typical individual with absolute eGFR of 124\u2005mL\/min and TBW of 70\u2005kg. PTA analyses demonstrated that the anticipated efficacious dose (30\u2005mg\/kg daily, 30\u2005min intravenous infusion) reaches a probability of 96.4% for a free AUC\/MIC target of 40, given an MIC of 8\u2005mg\/L, in a virtual Phase II patient population with an absolute eGFR extrapolated to 80\u2005mL\/min.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The results support further Phase II clinical trials with apramycin at an anticipated efficacious dose of 30\u2005mg\/kg once daily.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac225","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T15:21:50Z","timestamp":1658157710000},"page":"2718-2728","source":"Crossref","is-referenced-by-count":28,"title":["Population pharmacokinetics of apramycin from first-in-human plasma and urine data to support prediction of efficacious 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