What are the pharmacokinetic differences between Paxil (paroxetine) and Paxil CR (controlled-release paroxetine)?

From the Guidelines

Paxil CR offers a more consistent and stable pharmacokinetic profile compared to immediate-release Paxil, with fewer side effects and improved tolerability, due to its controlled-release mechanism and delayed absorption profile. The key pharmacokinetic difference between Paxil and Paxil CR lies in their absorption profiles: Paxil is absorbed rapidly with peak plasma concentrations occurring within 5-8 hours, while Paxil CR uses an enteric coating and controlled-release technology that delays initial absorption and then provides gradual release over approximately 4-5 hours 1. This results in Paxil CR reaching maximum concentration in about 6-10 hours with less pronounced peak levels. Both formulations have similar elimination half-lives of approximately 21 hours, allowing for once-daily dosing 1.

Some key points to consider when comparing Paxil and Paxil CR include:

• The controlled-release mechanism of Paxil CR helps reduce initial gastrointestinal side effects like nausea that are common with standard Paxil by avoiding the rapid rise in blood concentration 1.
• Paxil CR may provide more stable blood levels throughout the day, potentially improving tolerability while maintaining similar overall drug exposure 1.
• Patients switching between formulations should note that dosing equivalence is different - typically 25mg of Paxil CR corresponds to 20mg of immediate-release Paxil.
• Higher SSRI dosing, including fluoxetine and paroxetine, has been associated with higher dropout rates due to adverse effects, highlighting the importance of careful dosing and monitoring 1.

Overall, the pharmacokinetic differences between Paxil and Paxil CR can have significant implications for patient tolerability, adherence, and treatment outcomes, and should be carefully considered when selecting a treatment regimen 1.

From the Research

Pharmacokinetic Differences

• The pharmacokinetic differences between Paxil (paroxetine) and Paxil CR (controlled-release paroxetine) are related to their release mechanisms and bioavailability 2.
• Paxil CR is designed to provide a controlled-release of paroxetine, which can lead to a more consistent and sustained plasma concentration of the drug compared to the immediate-release formulation of Paxil 3.
• The controlled-release formulation of Paxil CR can reduce the peak-to-trough fluctuations in plasma concentrations, which may improve tolerability and reduce the risk of side effects 3.
• Studies have shown that the pharmacokinetic profiles of Paxil CR and Paxil are similar, with no significant differences in peak-reaching time (Tmax), peak concentration (Cmax), and the area under the blood level-time curve (AUC0-48) 2.

Bioavailability and Absorption

• Paroxetine is well absorbed from the gastrointestinal tract, with a bioavailability of approximately 30-60% due to partial first-pass metabolism 4.
• The bioavailability of Paxil CR is similar to that of Paxil, with a relative bioavailability of 97.97% 2.
• The controlled-release formulation of Paxil CR can provide a more consistent and sustained release of paroxetine, which may improve bioavailability and reduce the risk of side effects 3.

Elimination and Metabolism

• Paroxetine is eliminated after transformation in the liver into pharmacologically inactive metabolites, with a high affinity to the cytochrome P450 isoenzyme CYP2D6 4.
• The elimination half-life of paroxetine is approximately one day, with no significant differences between Paxil CR and Paxil 4, 5.
• The metabolism of paroxetine can be affected by other drugs that are metabolized via the same isoenzyme, which may lead to drug interactions 4.