Comment
Author: Admin | 2025-04-28
Rats, rabbits, or monkeys.ExcretionPregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug with a mean elimination half-life of 6.3 hours in subjects with normal renal function. Mean renal clearance was estimated to be 67.0 to 80.9 mL/min in young healthy subjects. Because pregabalin is not bound to plasma proteins this clearance rate indicates that renal tubular reabsorption is involved. Pregabalin elimination is nearly proportional to CLcr [see DOSAGE AND ADMINISTRATION].Specific PopulationsAge: Geriatric PatientsPregabalin oral clearance tended to decrease with increasing age. This decrease in pregabalin oral clearance is consistent with age-related decreases in CLcr. Reduction of pregabalin dose may be required in patients who have age-related compromised renal function [see DOSAGE AND ADMINISTRATION].SexPopulation pharmacokinetic analyses of the clinical studies showed that the relationship between daily dose and LYRICA CR drug exposure is similar between genders.Race/EthnicityIn population pharmacokinetic analyses of the clinical studies of LYRICA and LYRICA CR, the pharmacokinetics of pregabalin were not significantly affected by race (Caucasians, Blacks, and Hispanics).Renal ImpairmentPregabalin clearance is nearly proportional to CLcr. Dosage reduction in patients with reduced renal function is necessary. Pregabalin is effectively removed from plasma by hemodialysis. Following a 4-hour hemodialysis treatment, plasma pregabalin concentrations are reduced by approximately 50%. For patients on hemodialysis, treatment with LYRICA CR is not recommended [see DOSAGE AND ADMINISTRATION].Drug Interaction StudiesIn Vitro StudiesIn vitro studies showed that pregabalin is unlikely to be involved in significant pharmacokinetic drug interactions. Pregabalin, at concentrations that were, in general, 10-times those attained in clinical trials, does not inhibit human CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 enzyme systems. In vitro drug interaction studies demonstrate that pregabalin does not induce CYP1A2 or CYP3A4 activity. Therefore, an increase in the metabolism of co-administered CYP1A2 substrates (e.g., theophylline, caffeine) or CYP3A4 substrates (e.g., midazolam, testosterone) is not anticipated.In Vivo StudiesWith the exception of erythromycin, the interactions of LYRICA CR with co-administration of other drugs have not been systematically evaluated.Additional studies have been performed with LYRICA [see DRUG INTERACTIONS]. No pharmacokinetic interactions were observed between LYRICA and carbamazepine, ethanol, gabapentin, lamotrigine, lorazepam, oral contraceptive, oxycodone, phenobarbital, phenytoin, topiramate, and valproic acid. A similar lack of pharmacokinetic interactions would be expected to occur with LYRICA CR.The drug interaction studies described in this section were conducted in healthy adults, and across various patient populations.ErythromycinMultiple-dose administration of erythromycin (500 mg every 6 hours for 18 hours) in healthy subjects resulted
Add Comment