Dose-Related Reduction in Bupropion Plasma Concentrations by Ritonavir

The effect of repeat oral doses of ritonavir, at high (600 mg twice daily) and low (100 mg twice daily) doses, on the pharmacokinetics of a single dose of bupropion was evaluated in healthy volunteers. Subjects received a single dose of 150 mg of bupropion on day 1 and twice‐daily ritonavir from day 8 through day 30. Ritonavir was up‐titrated from 300 mg twice daily to 600 mg twice daily in the high‐dose ritonavir study, whereas subjects remained on 100 mg twice‐daily ritonavir in low‐dose ritonavir study. Subjects received a second single dose of bupropion on day 24. Serial blood samples were obtained to evaluate the pharmacokinetics of bupropion and its metabolites on days 1 and 24. Steady‐state ritonavir led to a decrease of area under the curve and maximum plasma concentration of bupropion by 62% to 67% in the high‐dose study and by 21 % to 22% in the low‐dose study, indicating a drug interaction of statistical and clinical significance, particularly at high doses of ritonavir. These studies demonstrate that the reduction of bupropion exposure by ritonavir is dose‐related. Dosage adjustment of bupropion may be needed when administered with ritonavir. However, the maximum recommended daily dose of bupropion should not be exceeded.