{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:10:24Z","timestamp":1784193024508,"version":"3.55.0"},"reference-count":11,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[1999,3,1]],"date-time":"1999-03-01T00:00:00Z","timestamp":920246400000},"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":[[1999,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Pleconaril is an orally active, broad-spectrum antipicornaviral agent which demonstrates excellent penetration into the central nervous system, liver, and nasal epithelium. In view of the potential pediatric use of pleconaril, we conducted a single-dose, open-label study to characterize the pharmacokinetics of this antiviral agent in pediatric patients. Following an 8- to 10-h period of fasting, 18 children ranging in age from 2 to 12 years (7.5 \u00b1 3.1 years) received a single 5-mg\/kg of body weight oral dose of pleconaril solution administered with a breakfast of age-appropriate composition. Repeated blood samples (\n            <jats:italic>n<\/jats:italic>\n            = 10) were obtained over 24 h postdose, and pleconaril was quantified from plasma by gas chromatography. Plasma drug concentration-time data for each subject were fitted to the curve by using a nonlinear, weighted (weight = 1\/\n            <jats:italic>Y<\/jats:italic>\n            <jats:sub>calc<\/jats:sub>\n            ) least-squares algorithm, and model-dependent pharmacokinetic parameters were determined from the polyexponential parameter estimates. Pleconaril was well tolerated by all subjects. A one-compartment open-model with first-order absorption best described the plasma pleconaril concentration-time profile in 13 of the subjects over a 24-h postdose period. Pleconaril pharmacokinetic parameters (means \u00b1 standard deviations) for these 13 patients were as follows. The maximum concentration of the drug in serum (\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            ) was 1,272.5 \u00b1 622.1 ng\/ml. The time to\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            was 4.1 \u00b1 1.5 h, and the lag time was 0.75 \u00b1 0.56 h. The apparent absorption rate constant was 0.75 \u00b1 0.48 1\/h, and the elimination rate constant was 0.16 \u00b1 0.07 1\/h. The area under the concentration-time curve from 0 to 24 h was 8,131.15 \u00b1 3,411.82 ng\u2009\u00b7\u2009h\/ml. The apparent total plasma clearance was 0.81 \u00b1 0.86 liters\/h\/kg, and the apparent steady-state volume of distribution was 4.68 \u00b1 2.02 liters\/kg. The mean elimination half-life of pleconaril was 5.7 h. The mean plasma pleconaril concentrations at both 12 h (250.4 \u00b1 148.2 ng\/ml) and 24 h (137.9 \u00b1 92.2 ng\/ml) after the single 5-mg\/kg oral dose in children were higher than that from in vitro studies reported to inhibit &gt;90% of nonpolio enterovirus serotypes (i.e., 70 ng\/ml). Thus, our data support the evaluation of a 5-mg\/kg twice-daily oral dose of pleconaril for therapeutic trials in pediatric patients with enteroviral infections.\n          <\/jats:p>","DOI":"10.1128\/aac.43.3.634","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:34:19Z","timestamp":1539045259000},"page":"634-638","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":35,"title":["Single-Dose Pharmacokinetics of a Pleconaril (VP63843) Oral Solution in Children and Adolescents"],"prefix":"10.1128","volume":"43","author":[{"given":"Gregory L.","family":"Kearns","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Sections of Pediatric Clinical Pharmacology and Experimental Therapeutics,1"},{"name":"<!--label omitted: 2-->Departments of Pediatrics,2"},{"name":"<!--label omitted: 3-->Pharmacology,3 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Abdel-Rahman","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Sections of Pediatric Clinical Pharmacology and Experimental Therapeutics,1"},{"name":"<!--label omitted: 2-->Departments of Pediatrics,2"},{"name":"<!--label omitted: 4-->Pharmacy Practice,4 University of Missouri\u2014Kansas City, Kansas City, Missouri;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura P.","family":"James","sequence":"additional","affiliation":[{"name":"<!--label omitted: 5-->Sections of Clinical Pharmacology and Toxicology,5"},{"name":"<!--label omitted: 6-->Emergency Medicine,6 and"},{"name":"<!--label omitted: 7-->Department of Pediatrics, University of Arkansas for Medical Sciences,7 Little Rock, Arkansas; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas L.","family":"Blowey","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Sections of Pediatric Clinical Pharmacology and Experimental Therapeutics,1"},{"name":"<!--label omitted: 8-->Pediatric Nephrology,8 and"},{"name":"<!--label omitted: 2-->Departments of Pediatrics,2"},{"name":"<!--label omitted: 3-->Pharmacology,3 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Marshall","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Sections of Pediatric Clinical Pharmacology and Experimental Therapeutics,1"},{"name":"<!--label omitted: 9-->Pediatric Critical Care Medicine,9 The Children\u2019s Mercy Hospital, Kansas City, Missouri;"},{"name":"<!--label omitted: 2-->Departments of Pediatrics,2"},{"name":"<!--label omitted: 3-->Pharmacology,3 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Wells","sequence":"additional","affiliation":[{"name":"<!--label omitted: 5-->Sections of Clinical Pharmacology and Toxicology,5"},{"name":"<!--label omitted: 10-->Nephrology,10"},{"name":"<!--label omitted: 7-->Department of Pediatrics, University of Arkansas for Medical Sciences,7 Little Rock, Arkansas; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard F.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"<!--label omitted: 11-->Infectious Disease,11 Arkansas Children\u2019s Hospital, and"},{"name":"<!--label omitted: 7-->Department of Pediatrics, University of Arkansas for Medical Sciences,7 Little Rock, Arkansas; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The Pediatric Pharmacology Research Unit Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.10.2706"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/20.5.1201"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/168.4.888"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-199601000-00015"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0095-5108(18)30192-1"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.46.100192.003223"},{"key":"e_1_3_2_8_2","unstructured":"Phoenix International Life Sciences\n          Validation of a high resolution gas chromatographic method for the determination of VP 63843 in human plasma by electron capture detection. Phoenix Project no. 952145\/EJN.\n          1996\n          Phoenix International Life Sciences\n          Montreal Quebec Canada"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/20.4.971"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/153.2.346"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3109\/00365549409011792"},{"key":"e_1_3_2_12_2","unstructured":"ViroPharma Incorporated. VP63843 Clinical Investigators Brochure. ViroPharma Incorporated Malvern Pa."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.43.3.634","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.43.3.634","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T16:03:06Z","timestamp":1645459386000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.43.3.634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,3]]},"references-count":11,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1999,3]]}},"alternative-id":["10.1128\/AAC.43.3.634"],"URL":"https:\/\/doi.org\/10.1128\/aac.43.3.634","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,3]]},"assertion":[{"value":"1998-03-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-12-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-03-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}