{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:00:50Z","timestamp":1792670450036,"version":"4.5.0"},"reference-count":24,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T00:00:00Z","timestamp":1749254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Anesthesia"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pentazocine is used for postoperative pain but is known to cause respiratory depression. Although hepatic metabolic activity in children gradually reaches adult levels, the effect of multiple doses in children with decreased clearance has not been elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>The objective of this study is to evaluate respiratory depression caused by pentazocine using a pharmacokinetic<jats:bold>\u2013<\/jats:bold>pharmacodynamic model and to optimize the dosing frequency to maintain target concentrations for analgesia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The pharmacokinetic model used the parameters of the three\u2010compartment model reported by Hamunen et\u00a0al. Pharmacodynamic parameters were estimated through sequential analysis, with the pharmacokinetic parameters fixed. Mean respiratory rate and oxygen saturation data were collected from Hamunen et\u00a0al. after the administration of 0.5\u2009mg\/kg pentazocine. The pharmacodynamic model was a turnover model in which the plasma pentazocine concentration affected the respiratory rate and oxygen saturation. We used the pharmacokinetic<jats:bold>\u2013<\/jats:bold>pharmacodynamic model to simulate changes in respiratory rate and oxygen saturation after 0.5\u2009mg\/kg pentazocine at 2\u2010, 4\u2010, and 6\u2010h dosing intervals. We also simulated cases with 20% and 40% decreased clearance. Pain relief was assessed using our previous model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After a single dose, respiratory rate dropped with a delayed response to the plasma concentration, reaching a minimum within 15 to 30\u2009min and falling below the normal range. It returned to baseline after about 75\u2009min. With multiple dosing, respiratory rate and oxygen saturation considerably decreased every 2\u2009h, regardless of clearance changes. At a 4\u2010h interval, respiratory depression occurred due to decreased clearance, whereas at a 6\u2010h interval, it was minimal. Pain was well controlled at 2\u2010, 4\u2010, and 6\u2010h dosing intervals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This pharmacokinetic\u2013pharmacodynamic modeling study supports a 6\u2010h dosing interval for pentazocine at 0.5\u2009mg\/kg in children. This interval strikes a balance between achieving effective analgesia and minimizing the risk of respiratory depression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pan.15135","type":"journal-article","created":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T11:18:47Z","timestamp":1749295127000},"page":"732-739","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pentazocine Pharmacodynamics in Children: Simulations to Assess Safety and Effectiveness"],"prefix":"10.1111","volume":"35","author":[{"given":"Takayuki","family":"Omori","sequence":"first","affiliation":[{"name":"Department of Pharmacy St. Luke's International Hospital  Tokyo Japan"},{"name":"Laboratory of Clinical Pharmacometrics School of Pharmacy, Nihon University  Chiba Japan"},{"name":"Division of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Nihon Pharmaceutical University  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6111-8537","authenticated-orcid":false,"given":"Takahiko","family":"Aoyama","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacometrics School of Pharmacy, Nihon University  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7967-2947","authenticated-orcid":false,"given":"Yasuhiro","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacometrics School of Pharmacy, Nihon University  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60245-6"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/pan.13373"},{"key":"e_1_2_10_4_1","unstructured":"Administration USFaD \u201cFDA Drug Safety Communication: FDA Restricts Use of Prescription Codeine Pain and Cough Medicines Andtramadol Pain Medicines in Children; Recommends Against Use in Breastfeeding Women \u201daccessed March 23 2024 https:\/\/www.fda.gov\/drugs\/drug\u2010safety\u2010and\u2010availability\/fda\u2010drug\u2010safety\u2010communication\u2010fda\u2010restricts\u2010use\u2010prescription\u2010codeine\u2010pain\u2010and\u2010cough\u2010medicines\u2010and."},{"issue":"4","key":"e_1_2_10_5_1","first-page":"443","article-title":"Pentazocine Versus Pentazocine With Rectal Diclofenac for Postoperative Pain Relief After Cesarean Section\u2010 a Double Blind Randomized Placebo Controlled Trial in a Low Resource Area","volume":"23","author":"Olateju S. 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