Pharmacokinetics of Oral Doses of Telmisartan and Nisoldipine, Given Alone and in Combination, in Patients With Essential Hypertension

Abstract

This randomized, single-blind, parallel-group study was performed to assess pharmacokinetic interactions potentially occurring during concomitant use of telmisartan and nisoldipine. Patients with essential hypertension (n = 37) were treated with once-daily doses of telmisartan, nisoldipine, or their combination for 6 weeks. The regimen was started at low dose with an increase of dosage after 3 weeks of treatment. AUC(ss) (132%; P < .01) of telmisartan applied in doses of 80 mg was significantly higher after concomitant application with nisoldipine (10 mg), whereas CL/f(ss) (-54%; P < .05) and Vz/f(ss) (-72%; P < .05) were significantly lower. Regarding pharmacokinetic parameters of nisoldipine, significant differences between treatment groups were not detected. In conclusion, the results of this study strongly suggest that concomitant treatment with nisoldipine enhances telmisartan bioavailability in hypertensive individuals. Larger crossover trials will have to establish these observations and investigate whether interaction of both drugs affects telmisartan efficacy and tolerability in clinical use.

A Systematic Comparison of the Properties of Clinically Used Angiotensin II Type 1 Receptor Antagonists

“…Because of the possible additive pharmacokinetic effect, concomitant use of telmisartan and ramipril is not recommended. Although concomitant administration of telmisartan did not affect the pharmacokinetics of nisoldipine, nisoldipine increased the AUC and reduced the clearance of telmisartan in patients with hypertension (Bajcetic et al, 2007). Exposure to mycophenolate mofetil was reported to be lower in renal transplant patients upon concomitant administration of telmisartan, possibly because the metabolism of mycophenolate mofetil involves uridine diphosphate-glucuronosyltransferase 1A9, which has been identified as a PPAR-g target gene .…”

UGT1A3 and Sex Are Major Determinants of Telmisartan Pharmacokinetics—A Comprehensive Pharmacogenomic Study

“…Interestingly, nisoldipine has increased the AUC of telmisartan by 132%. 37 In human liver microsomes, nisoldipine inhibits the glucuronidation of estradiol, 38 mediated by UGT1A1, UGT1A3, UGT1A8, UGT1A10, and UGT2B7. 39 Further studies are required to determine whether nisoldipine inhibits UGT1A3.…”

Interaction of angiotensin receptor type 1 blockers with ATP‐binding cassette transporters

“…For instance, only approximately 15% of the bioavailable amount of the ARB telmisartan is metabolised by direct glucuronidation [10]. However, we recently demonstrated that the kinetics of telmisartan are substantially altered by the calcium channel blocker nisoldipine [11] suggesting that alternative pharmacokinetic pathways, such as ABC-transporters, may be used by this ARB. Moreover, the metabolite telmisartan acylglucuronide has been identified as a substrate of P-gp, BCRP and MRP2 [12] and genetic polymorphisms of MRP2 appear to influence inter-individual variability of telmisartan pharmacokinetics [13].…”