Tenofovir Disoproxil Fumarate + Dolutegravir = Precautionary

Study Design

This was an open-label, repeat dose, 3-period, drug-drug interaction study in 15 healthy subjects. The mean age was 39 years old and 94% of the subjects were male. During the three dosing periods, subjects received the following treatments: 50mg of dolutegravir daily for 5 days in period 1, followed by a washout of at least 6 days. In period 2, subjects received tenofovir DF 300mg daily for 7 days. With no washout, period 2 was then followed by coadministration of dolutegravir 50mg daily and tenofovir DF 300mg daily for 5 days in period 3. Pharmacokinetic (PK) sampling was performed on the last day of dosing in each treatment period, to 24 hours post dose. PK parameters that were calculated included area under the concentration-time profile from time zero to the end of the dosage interval [AUC(0-t)], the maximum observed plasma concentration (Cmax), and the plasma concentration at the end of the dosing interval (Ct). Statistical analysis was preformed on log-transformed PK parameters. Analysis of variance was used to assess the effect of tenofovir DF on the PK of dolutegravir and vice versa, the effect of dolutegravir on the PK of tenofovir. The ratio of geometric least squares means and associated 90% confidence interval was estimated for the PK parameters

Study Results

Coadministration of tenofovir DF and dolutegravir, had no significant effect on the PK of dolutegravir. Coadministration of these two drugs did result in a 19% increase in the mean tenofovir trough plasma concentration. However, the authors did not consider this increase clinically significant. The authors stated that because the mean AUC(0-t) of tenofovir with and without dolutegravir were virtually superimposable, this demonstrated that the interaction was not significant. The author's recommendation is that at this dose of dolutegavir, the drug does not interact with tenofovir DF. Therefore, both drugs can be given together without dose adjustment.

Study Conclusions

References

Ivy Song, Sherene S Min, Julie Borland, Yu Lou, Shuguang Chen, Toru Ishibashi, Toshihiro Wajima, Stephen C Piscitelli. Lack of interaction between the hiv integrase inhibitor s/gsk1349572 and tenofovir in healthy subjects. Jaids Journal Of Acquired Immune Deficiency Syndromes. 2010; 3: 365-367.