Slide 21 of 76
Notes:
- Now being increasingly recognized as having a role in pharmacokinetics of many medications, including protease inhibitors
- oral absorption: oral bioavailability may be limited by the presence of CYP3A4 in the GI tract and liver (first-pass effect), as well as P-gp, which may transport absorbed drug back into the intestinal lumen
- CNS exposure: in addition to other factors such as lipophilicity, plasma protein binding, molecular weight, and concentration, P-gp may play a significant role in limiting penetration of protease inhibitors into the brain
- Agents which inhibit P-gp may affect dispostion of P-gp substrates (e.g., ritonavir inhibits P-gp; may partially account for its profound effect on saquinavir metabolism)
Metheny CJ, Lamb MW, Brouwer KLR, Pollack GM. Pharmacokinetic and Pharmacodynamic Implications of P-glycoprotein Modulation. Pharmacotherapy 2001; 21(7):778-796.
