FDC of Telmisartantan with Rosuvastain/Ezetimibe increases systemic exposure of Telmisartan and Rosuvastatin: study

Among statins, rosuvastatin is the most efficacious and is relatively safe, with low rates of severe myopathy, rhabdomyolysis and renal failure. Ezetimibe biotransforms to ezetimibe glucuronide, which is an active metabolite in the intestinal mucosa and liver, blocks the cholesterol absorption in the small intestine. Telmisartan, rosuvastatin and ezetimibe are commonly recommended as combination therapies. However, the pharmacokinetic (PK) interaction among these therapeutic drugs has not been clearly reported. Therefore, Dr Chang Hee Kim and colleagues conducted a study to investigate possible interactions between telmisartan monotherapy and a fixed-dose combination (FDC) of rosuvastatin/ezetimibe.

It was a randomized, open-label, multiple oral dose, three-treatment, three-period, six-sequence crossover study in healthy male volunteers. Researchers administered monotherapy and co-therapy with telmisartan (80 mg) or an FDC of rosuvastatin and ezetimibe (20/10 mg) and compared after once-daily treatment for 7 days. They evaluated the pharmacokinetic (PK) profiles for telmisartan, rosuvastatin, total ezetimibe (ezetimibe + ezetimibe glucuronide) and ezetimibe up to 48 h after the last dose. They determined 14 days washout period between each treatment. The major outcome assessed was the geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for the peak plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve during the dosing interval at steady state (AUCτ,ss).

Key findings of the study were:

♦ Upon analysis, researchers have found that the GMR (90% CI) of Cmax,ss and AUCτ,ss were:

          • 1.258 and 1.264 for telmisartan,

          • 0.796 and 0.904 for total ezetimibe,

          • 1.237 and 0.988 for ezetimibe and

          • 2.616 and 1.265 for rosuvastatin.

♦ They reported no serious adverse events or clinically significant results.

The authors concluded, "The coadministration of multiple doses of telmisartan and rosuvastatin/ezetimibe led to a mild increase in systemic exposure with respect to telmisartan and rosuvastatin and a nonsignificant change in exposure to total ezetimibe and ezetimibe, which was not considered clinically significant without safety concerns" and further added, "For the generalizability of the clinical effects, a large-scale clinical study might be required in patients with hypertension and dyslipidemia".

For further information:

https://link.springer.com/article/10.1007%2Fs12325-020-01592-8