Pharmacokinetics of oral doses of telmisartan and nisoldipine, given alone and in combination, in patients with essential hypertension.
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.
Bajcetic
Milica
M
Institute of Experimental and Clinical Pharmacology and Toxicology, Clinical Pharmacology Unit, University Hospital Hamburg-Eppendorf, Martinistrasse 521, D-20246 Hamburg.
Benndorf
Ralf A
RA
Appel
Daniel
D
Schwedhelm
Edzard
E
Schulze
Friedrich
F
Riekhof
Daniel
D
Maas
Renke
R
Böger
Rainer H
RH
D000284:Administration, Oral; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D001562:Benzimidazoles / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001565:Benzoates / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004487:Edema / Q000139:chemically induced; D005260:Female; D006207:Half-Life; D006261:Headache / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015737:Nisoldipine / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016037:Single-Blind Method; D000077333:Telmisartan; D013997:Time Factors
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D002121:Calcium Channel Blockers; D015737:Nisoldipine; D000077333:Telmisartan