{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:29:20Z","timestamp":1792441760495,"version":"4.5.0"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T00:00:00Z","timestamp":1414800000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Serum penicillin G falls to low levels 2 weeks after injection as benzathine penicillin G (BPG) in young adults. Using Pmetrics and previously reported penicillin G pharmacokinetic data after 1.2 million units were given as BPG to 329 male military recruits, here we develop the first reported population pharmacokinetic model of penicillin G after BPG injection. We simulated time-concentration profiles over a broad range of pediatric and adult weights after alternative doses and dose frequencies to predict the probability of maintaining serum penicillin G concentrations of &gt;0.02 mg\/liter, a proposed protective threshold against group A\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Streptococcus pyogenes<\/jats:named-content>\n            (GAS). The final population model included linear absorption into a central compartment, distribution to and from a peripheral compartment, and linear elimination from the central compartment, with allometrically scaled volumes and rate constants. With 1.2 million units of BPG given intramuscularly every 4 weeks in four total doses, only 23.2% of 5,000 simulated patients maintained serum penicillin G trough concentrations of &gt;0.02 mg\/liter 4 weeks after the last dose. When the doses were 1.8 million units and 2.4 million units, the percentages were 30.2% and 40.7%, respectively. With repeated dosing of 1.2 million units every 3 weeks and every 2 weeks for 4 doses, the percentages of simulated patients with a penicillin G trough concentration of &gt;0.02 mg\/liter were 37.8% and 65.2%, respectively. Our simulations support recommendations for more frequent rather than higher BPG doses to prevent recurrent rheumatic heart disease in areas of high GAS prevalence or during outbreaks.\n          <\/jats:p>","DOI":"10.1128\/aac.02744-14","type":"journal-article","created":{"date-parts":[[2014,9,3]],"date-time":"2014-09-03T12:54:02Z","timestamp":1409748842000},"page":"6735-6741","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["A Population Pharmacokinetic Modeling Approach Shows that Serum Penicillin G Concentrations Are Below Inhibitory Concentrations by Two Weeks after Benzathine Penicillin G Injection in the Majority of Young Adults"],"prefix":"10.1128","volume":"58","author":[{"given":"Michael","family":"Neely","sequence":"first","affiliation":[{"name":"Laboratory of Applied Pharmacokinetics and Bioinformatics, Children's Hospital of Los Angeles, and Keck School of Medicine of USC, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward L.","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L.","family":"Blumer","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis J.","family":"Faix","sequence":"additional","affiliation":[{"name":"Operational Infectious Diseases Department, Naval Health Research Center, San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Broderick","sequence":"additional","affiliation":[{"name":"Operational Infectious Diseases Department, Naval Health Research Center, San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1952.03680160021005"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025308"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1542\/peds.97.6.989","article-title":"Are the currently recommended doses of benzathine penicillin G adequate for secondary prophylaxis of rheumatic fever?","volume":"97","author":"Currie BJ","year":"1996","unstructured":"CurrieBJ. 1996. Are the currently recommended doses of benzathine penicillin G adequate for secondary prophylaxis of rheumatic fever? Pediatrics 97:989\u2013991.","journal-title":"Pediatrics"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(89)80352-X"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1093\/clinids\/22.4.727","article-title":"Serum levels of penicillin in basic trainees in the U.S. Army who received intramuscular penicillin G benzathine","volume":"22","author":"Bass JW","year":"1996","unstructured":"BassJWLongfieldJNJonesRGHartmannRM. 1996. Serum levels of penicillin in basic trainees in the U.S. Army who received intramuscular penicillin G benzathine. Clin. Infect. Dis. 22:727\u2013728.","journal-title":"Clin. Infect. Dis."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.108.5.1180"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e31825051d4"},{"key":"e_1_3_2_9_2","volume-title":"Technical report TR-2014-1","author":"Yamada WM","unstructured":"YamadaWMBartroffJBayardDSBurkeJVan GuilderMJelliffeRLearyRNeelyMNKryshchenkoASchumitzkyA. Accessed 1 May 2014. The nonparametric adaptive grid algorithm for population pharmacokinetic modeling. Technical report TR-2014-1. University of Southern California Laboratory of Applied Pharmacokinetics, Los Angeles, CA. http:\/\/www.lapk.org\/techReports.php."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31825c4ba6"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198710223171717"},{"key":"e_1_3_2_12_2","volume-title":"Model selection and multi-model inference","author":"Burnham KP","year":"2010","unstructured":"BurnhamKPAndersonDR. 2010. Model selection and multi-model inference. 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Three- versus four-week administration of benzathine penicillin G: effects on incidence of streptococcal infections and recurrences of rheumatic fever. Pediatrics 97:984\u2013988.","journal-title":"Pediatrics"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1542\/peds.97.6.992","article-title":"Rheumatic fever prophylaxis using benzathine penicillin G (BPG): two-week versus four-week regimens. Comparison of two brands of BPG","volume":"97","author":"Kassem AS","year":"1996","unstructured":"KassemASZaherSRAbou-ShleibHEl-KholyAGMadkourAAKaplanEL. 1996. Rheumatic fever prophylaxis using benzathine penicillin G (BPG): two-week versus four-week regimens. Comparison of two brands of BPG. 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