{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T00:04:28Z","timestamp":1700352268841},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T00:00:00Z","timestamp":1362700800000},"content-version":"vor","delay-in-days":4084,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:p>The effects of drug\u2010drug interactions on clonazepam clearance were examined through a retrospective analysis of serum concentration data from pediatric and adult epileptic patients. Patients received clonazepam as monotherapy or in combination with other antiepileptic drugs. A total of259 serum clonazepam concentrations gathered from 137 patients were used in a population analysis of drug\u2010drug interactions on clonazepam clearance. Data were analyzed using a nonlinear mixed\u2010effects modeling (NONMEM) technique. The final model describing clonazepam clearance was CL = 152 \u00b7 TBW<jats:sup>\u22120.181<\/jats:sup> \u00b7 DIF, where CL is clearance (ml\/kg\/h), TBWis total body weight (kg), and DIF (drug interaction factor) is a scaling factor for concomitant medication with a value of 1 for patients on clonazepam monotherapy, 1.18 for those patients receiving concomitant administration of clonazepam and one antiepileptic drug (carbamazepine or valproic acid), and 2.12 \u00b7 TBW<jats:sup>\u22120119<\/jats:sup> for those patients receiving concomitant administration of clonazepam and more than two antiepileptic drugs. Clonazepam clearance decreased in a weight\u2010related fashion in children, with minimal changes observed in adults. Concomitant administration of clonazepam and carbamazepine resulted in a 22% increase in clonazepam clearance. Concomitant administration of clonazepam and valproic acid resulted in a 12% increase in clonazepam clearance. Concomitant administration of clonazepam with two or more antiepileptic drugs resulted in a 23% to 75% increase in clonazepam clearance.<\/jats:p>","DOI":"10.1177\/0091270002042001009","type":"journal-article","created":{"date-parts":[[2003,4,28]],"date-time":"2003-04-28T10:36:11Z","timestamp":1051526171000},"page":"81-88","source":"Crossref","is-referenced-by-count":7,"title":["Pharmacoepidemiologic Investigation of Clonazepam Relative Clearance by Mixed\u2010Effect Modeling Using Routine Clinical Pharmacokinetic Data in Japanese 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