Population pharmacokinetics of perhexiline from very sparse, routine monitoring data

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dc.contributor.authorHussein, R.
dc.contributor.authorCharles, B.
dc.contributor.authorMorris, R.
dc.contributor.authorRasiah, R.
dc.date.issued2001
dc.description.abstractUsing NONMEM, the population pharmacokinetics of perhexiline were studied in 88 patients (34 F, 54 M) who were being treated for refractory angina. Their mean +/- SD (range) age was 75 +/- 9.9 years (46-92), and the length of perhexiline treatment was 56 +/- 77 weeks (0.3-416). The sampling time after a dose was 14.1 +/- 21.4 hours (0.5-200), and the perhexiline plasma concentrations were 0.39 +/- 0.32 mg/L (0.03-1.56). A one-compartment model with first-order absorption was fitted to the data using the first-order (FO) approximation. The best model contained 2 subpopulations (obtained via the $MIXTURE subroutine) of 77 subjects (subgroup A) and 11 subjects (subgroup B) that had typical values for clearance (CL/F) of 21.8 L/h and 2.06 L/h, respectively. The volumes of distribution (V/F) were 1470 L and 260 L, respectively, which suggested a reduction in presystemic metabolism in subgroup B. The interindividual variability (CV%) was modeled logarithmically and for CL/F ranged from 69.1% (subgroup A) to 86.3% (subgroup B). The interindividual variability in V/F was 111%. The residual variability unexplained by the population model was 28.2%. These results confirm and extend the existing pharmacokinetic data on perhexiline, especially the bimodal distribution of CL/F manifested via an inherited deficiency in hepatic and extrahepatic CYP2D6 activity.
dc.identifier.citationTherapeutic Drug Monitoring, 2001; 23(6):636-643
dc.identifier.doi10.1097/00007691-200112000-00007
dc.identifier.issn0163-4356
dc.identifier.issn1536-3694
dc.identifier.urihttp://hdl.handle.net/2440/14567
dc.language.isoen
dc.publisherLippincott Williams & Wilkins
dc.source.urihttps://doi.org/10.1097/00007691-200112000-00007
dc.subjectHumans
dc.subjectPerhexiline
dc.subjectCytochrome P-450 CYP2D6
dc.subjectVasodilator Agents
dc.subjectDrug Monitoring
dc.subjectMetabolic Clearance Rate
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.titlePopulation pharmacokinetics of perhexiline from very sparse, routine monitoring data
dc.typeJournal article
pubs.publication-statusPublished

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