{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T05:38:16Z","timestamp":1773293896575,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,6,9]],"date-time":"2011-06-09T00:00:00Z","timestamp":1307577600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:p><jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold><\/jats:p><jats:p>\u2022\u2003Pregabalin has been approved in many countries for partial\u2010onset seizures, generalized anxiety disorder and a wide variety of pain disorders.<\/jats:p><jats:p>\u2022\u2003Although pharmacokinetic studies have demonstrated that pregabalin apparent clearance is correlated with estimated creatinine clearance, quantitatively accurate estimation of this relationship is warranted for establishing clinical usage of this drug.<\/jats:p><jats:p><jats:bold>WHAT THIS STUDY ADDS<\/jats:bold><\/jats:p><jats:p>\u2022\u2003A population pharmacokinetic model was developed from 14 pregabalin clinical trials using the first\u2010order conditional estimation method, where a one\u2010compartment model with first\u2010order absorption and elimination adequately described pregabalin pharmacokinetics.<\/jats:p><jats:p>\u2022\u2003Based on the developed model, pregabalin systemic exposure in patients with lower renal function (30 \u2264 estimated creatinine clearance [CL<jats:sub>cr<\/jats:sub>] &lt;60\u2003ml\u2003min<jats:sup>\u22121<\/jats:sup>) is expected to be similar to exposure in patients with normal renal function (CL<jats:sub>cr<\/jats:sub>\u226560) administered twice the dose.<\/jats:p><jats:p>\u2022\u2003This study indicated that the systemic exposure of pregabalin could be adjusted with reference to the estimated proportional relationship between pregabalin apparent clearance and CL<jats:sub>cr<\/jats:sub>regardless of the disease.<\/jats:p><jats:p><jats:bold>AIM<\/jats:bold>Pregabalin, a chemical analogue of the mammalian neurotransmitter \u03b3\u2010aminobutyric acid, has been approved in many countries for partial\u2010onset seizures, generalized anxiety disorder and various other pain disorders, including neuropathic pain associated with post\u2010herpetic neuralgia and diabetic peripheral neuropathy and fibromyalgia. The aim of this study was to develop a population pharmacokinetic model and quantify the influence of covariates on the parameters.<\/jats:p><jats:p><jats:bold>METHODS<\/jats:bold>This pregabalin population pharmacokinetic analysis was conducted on data from 14 clinical trials involving healthy subjects, subjects with impaired renal function and patients with post\u2010herpetic neuralgia or diabetic peripheral neuropathy (<jats:italic>n<\/jats:italic>= 616). The data analysis was performed using nonlinear mixed effects modelling methodology as implemented by NONMEM.<\/jats:p><jats:p><jats:bold>RESULTS<\/jats:bold>A one\u2010compartment model with first\u2010order absorption and elimination adequately described pregabalin pharmacokinetics. The model indicated that pregabalin apparent clearance (CL\/<jats:italic>F<\/jats:italic>) was proportional to estimated creatinine clearance (CL<jats:sub>cr<\/jats:sub>). The pregabalin systemic exposure in patients with lower renal function who received pregabalin 150\u2003mg twice daily was almost equal to that of patients with normal renal function administered pregabalin 300\u2003mg twice daily. The systemic exposure stratified by lower or normal renal function was similar between patients with post\u2010herpetic neuralgia and diabetic peripheral neuropathy.<\/jats:p><jats:p><jats:bold>CONCLUSION<\/jats:bold>The developed model identified CL<jats:sub>cr<\/jats:sub>and ideal body weight as clinically influential covariates on CL\/<jats:italic>F<\/jats:italic>and volume of distribution, respectively. This study indicates that renal function accounts for variability in the apparent clearance of pregabalin which is consistent with what is known about the elimination of this drug.<\/jats:p>","DOI":"10.1111\/j.1365-2125.2011.03932.x","type":"journal-article","created":{"date-parts":[[2011,2,9]],"date-time":"2011-02-09T12:37:16Z","timestamp":1297255036000},"page":"63-76","source":"Crossref","is-referenced-by-count":28,"title":["Population pharmacokinetics of pregabalin in healthy subjects and patients with post\u2010herpetic neuralgia or diabetic peripheral 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